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WO2024130175A2 - Molécules de liaison à l'antigène qui se lient à des particules d'aav et utilisations - Google Patents

Molécules de liaison à l'antigène qui se lient à des particules d'aav et utilisations Download PDF

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Publication number
WO2024130175A2
WO2024130175A2 PCT/US2023/084372 US2023084372W WO2024130175A2 WO 2024130175 A2 WO2024130175 A2 WO 2024130175A2 US 2023084372 W US2023084372 W US 2023084372W WO 2024130175 A2 WO2024130175 A2 WO 2024130175A2
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seq
amino acid
acid sequence
hcvr
lcvr
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PCT/US2023/084372
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WO2024130175A3 (fr
Inventor
Christos Kyratsous
Andrew J. Murphy
Sven MOLLER-TANK
Yang Shen
Tri Nguyen
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Regeneron Pharmaceuticals, Inc.
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Publication of WO2024130175A2 publication Critical patent/WO2024130175A2/fr
Publication of WO2024130175A3 publication Critical patent/WO2024130175A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2851—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2881—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD71
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Definitions

  • the present disclosure relates to antigen-binding molecules, including antibodies or antigen-binding fragments thereof, that bind to a capsid of an adeno-associated virus (AAV) particle.
  • AAV adeno-associated virus
  • the disclosure provides multispecific antigen-binding molecules such as multispecific antibodies, e.g., bispecific antibodies, or antigen-binding fragments thereof, that bind to a capsid of an AAV and/or a molecule on a cell surface, as well as related molecular complexes and pharmaceutical compositions.
  • Methods for using the antibodies (e.g., multispecific antibodies) disclosed herein, molecular complexes and/or pharmaceutical composition are also provided.
  • Viral particles have emerged as vectors for gene therapy and the treatment of disease.
  • Viral vectors such as those based on the genome of adeno-associated virus (AAV)
  • AAV adeno-associated virus
  • retargeted AAV as a gene delivery vehicle remains less than ideal, at least in part, due to limited success from the efforts to redirect vector tropism.
  • the efficiency of AAV vector-mediated gene delivery to different cell types also varies greatly.
  • One possible mechanism for inefficient AAV transduction of certain cells may be a lack of cellular receptor(s) to mediate virus binding and entry.
  • the present disclosure provides antibodies that bind to a capsid of an adeno-associated virus (AAV) particle, and multispecific antibodies such as, for example, bispecific antibodies, which can bind both to the capsid of an AAV particle and a molecule (i.e., a target molecule) on a cell surface, and methods of use thereof.
  • AAV adeno-associated virus
  • multispecific antibodies such as, for example, bispecific antibodies, which can bind both to the capsid of an AAV particle and a molecule (i.e., a target molecule) on a cell surface
  • the antibodies described herein can bridge the virus to target cell surfaces that are not naturally targeted by the virus, thereby redirecting virus delivery and transduction.
  • an antibody, or an antigen-binding fragment thereof wherein said antibody, or said antigen-binding fragment thereof, binds to a capsid of an adeno- associated virus (AAV) particle, and wherein said antibody, or said antigen-binding fragment thereof, comprises: a) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a light chain variable region (LCVR) that comprises a LCDR1
  • HCVR2 a heavy chain variable region
  • said antibody, or said antigen-binding fragment thereof comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:
  • said antibody, or said antigen-binding fragment thereof comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; d) a HCVR comprising the amino acid sequence of SEQ ID NO: 42, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; e) a HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1159, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; f) a HCVR comprising the amino acid sequence of S
  • an antibody, or an antigen-binding fragment thereof wherein said antibody, or said antigen-binding fragment thereof, binds to a capsid of an adeno-associated virus (AAV) particle, wherein said antibody, or said antigen-binding fragment thereof, binds to one or more residues in one or more viral protein 3 (VP3) polypeptides in said capsid, wherein said one or more residues are selected from the residues listed in Tables 18-26.
  • AAV adeno-associated virus
  • said antibody, or said antigen-binding fragment thereof binds to a capsid of an AAV2 particle comprising amino acid substitutions R585A and R588A, and wherein the said one or more residues are selected from the following residues in said VP3 polypeptides (according to VP1 numbering): a) S264, A266, N268, H271 , N382, S384, Q385, G512, R487, D494, K527, D529, K532, L538, D533, E555, N705, K706, V708, T450, Q457, and R459; b) S264, G265, A266, S267, N268, H271 , N382, G383, S384, R487, K527, D528, E530, E574, Q575, K706, and S707; c) N254, L256, K258, I260, S261 , Q263, Y272,
  • said antibody, or said antigen-binding fragment thereof binds to a capsid of an AAV8 particle, and wherein the said one or more residues are selected from the following residues in said VP3 polypeptides (according to VP1 numbering): a) N255, L257, K259, 1261 , S262, N263, S266, A269, Y275, E325, V326, T327, Q328, A658, N670, S671 , F672, I673, T674, Q548, N549, A550, A551 , D559, E720, and T663; and/or b) N255, L257, S266, E325, V326, T327, Q328, N670, S671 , F672, I673, T674, N549, T719, and E720.
  • said antibody, or said antigen-binding fragment thereof binds to a capsid of an AAV9 particle, and wherein the said one or more residues are selected from the following residues in said VP3 polypeptides (according to VP1 numbering): a) N254, I260, N262, Y274, E324, V325, T326, D327, N328, R550, D665, N668, S669, F670, 1671 , T672, Q546, G547, G549, E718, and A661 ; and/or b) N254, L256, I260, N262, E324, V325, T326, D551 , N668, S669, F670, T672, G330, and E718.
  • said antibody, or said antigen-binding fragment thereof comprises:
  • HCVR heavy chain variable region
  • HCDR2 heavy chain variable region
  • LCVR light chain variable region
  • HCVR heavy chain variable region
  • HCDR2 heavy chain variable region
  • LCVR light chain variable region
  • HCVR heavy chain variable region
  • HCDR2 heavy chain variable region
  • LCVR light chain variable region
  • HCVR heavy chain variable region
  • HCDR2 HCDR2
  • HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 81
  • LCVR light chain variable region
  • said antibody, or said antigen-binding fragment thereof comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 83, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 87; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
  • said antibody, or said antigen-binding fragment thereof comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1159, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 71
  • LCVR comprising the amino acid sequence of SEQ ID NO: 10
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 81
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • said antibody, or said antigen-binding fragment thereof is a humanized antibody or antigen binding fragment thereof, human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, Fab fragment, F(ab')2 fragment, F(ab)'3 fragments, single-chain fragment variable (scFv), bis-scFv, (scFv)2, diabody, minibody, nanobody, triabody, tetrabody, disulfide stabilized Fv protein (dsFv), single-domain antibody (sdAb), Ig NAR, single heavy chain antibody, bispecific antibody, trispecific antibody, or chemically modified derivatives thereof.
  • said antibody, or said antigen-binding fragment thereof comprises an IgG 1 , lgG2, lgG3, or lgG4 constant region, or a variant thereof. [0018] In some embodiments, said antibody, or said antigen-binding fragment thereof, comprises an IgG 1 constant region, or a variant thereof.
  • the IgG 1 constant region comprises the amino acid sequence of SEQ ID NO: 259 or 1 164.
  • said antibody, or said antigen-binding fragment thereof comprises an lgG4 constant region, or a variant thereof.
  • the lgG4 variant comprises a hinge domain modified to reduce binding to Fey receptors.
  • the lgG4 constant region comprises the amino acid sequence of SEQ ID NO: 261.
  • said antigen-binding fragment is a Fab fragment.
  • said antigen-binding fragment is an scFv fragment.
  • said antibody, or said antigen-binding fragment thereof binds to AAV2 with a dissociation constant (KD) of less than about 1.5 x 10 -6 M, as measured in a surface plasmon resonance assay.
  • KD dissociation constant
  • said antibody, or said antigen-binding fragment thereof binds to AAV2 with a dissociation constant (K D ) of less than about 20 nM, as measured in a surface plasmon resonance assay.
  • K D dissociation constant
  • said capsid comprises one or more wild-type AAV capsid polypeptides.
  • said capsid comprises one or more non-wild-type AAV capsid polypeptides.
  • rein binding of said antibody or antigen-binding fragment thereof to said AAV particle capsid does not neutralize said AAV particle.
  • an antibody or an antigen-binding fragment thereof, that binds to the same epitope(s) as any of the above-described antibodies or antigenbinding fragments.
  • an antibody or an antigen-binding fragment thereof, that competes for binding to a capsid of an adeno-associated virus (AAV) particle with any of the above-described antibodies or antigen-binding fragments.
  • AAV adeno-associated virus
  • composition comprising any of the above-described antibodies or antigen-binding fragments and a pharmaceutically acceptable carrier or excipient.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: i) a first antigen-binding domain that binds to a capsid of an adeno-associated virus (AAV) particle; and ii) a second antigen-binding arm that binds to a molecule on a cell surface
  • said first antigen-binding domain comprises: a) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10;
  • a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 10
  • the first antigen-binding domain that binds to a capsid of an AAV particle comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:
  • the first antigen-binding domain that binds to a capsid of an AAV particle comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; d) a HCVR comprising the amino acid sequence of SEQ ID NO: 42, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; e) a HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1159, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: i) a first antigen-binding domain that binds to a capsid of an adeno-associated virus (AAV) particle, and ii) a second antigen-binding domain that binds to a molecule on a cell surface, wherein said first antigen-binding domain binds to one or more residues in one or more viral protein 3 (VP3) polypeptides in said capsid, wherein said one or more residues are selected from the residues listed in Tables 18-26.
  • AAV adeno-associated virus
  • said first antigen-binding domain binds to a capsid of an AAV2 particle comprising amino acid substitutions R585A and R588A, and wherein the said one or more residues are selected from the following residues in said VP3 polypeptides (according to VP1 numbering): a) S264, A266, N268, H271 , N382, S384, Q385, G512, R487, D494, K527, K529, K532, L538, D533, E555, N705, K706, V708, T450, Q457, and R459; b) S264, G265, A266, S267, N268, H271 , N382, G383, S384, R487, K527, D528, E530, Q574, Q575, K706, and S707; c) N254, L256, K258, I260, S261 , Q263, Y272, E322, V323,
  • said first antigen-binding domain binds to a capsid of an AAV8 particle, and wherein the said one or more residues are selected from the following residues in said VP3 polypeptides (according to VP1 numbering): e) N255, L257, K259, 1261 , S262, N263, S266, A269, Y275, E325, V326, T327, Q328, A658, N670, S671 , F672, I673, T674, Q548, N549, A550, A551 , D559, E720, and T663; and/or f) N255, L257, S266, E325, V326, T327, Q328, N670, S671 , F672, I673, T674, N549, T719, and E720.
  • said first antigen-binding domain binds to a capsid of an AAV9 particle, and wherein the said one or more residues are selected from the following residues in said VP3 polypeptides (according to VP1 numbering): g) N254, I260, N262, Y274, E324, V325, T326, D327, N328, R550, D665, N668, S669, F670, 1671 , T672, Q546, G547, G549, E718, and A661 ; and/or h) N254, L256, I260, N262, E324, V325, T326, D551 , N668, S669, F670, T672, G330, and E718.
  • said first antigen-binding domain that binds to a capsid of an AAV particle comprises:
  • HCVR heavy chain variable region
  • HCDR2 heavy chain variable region
  • LCVR light chain variable region
  • HCVR heavy chain variable region
  • HCDR2 heavy chain variable region
  • LCVR light chain variable region
  • HCVR heavy chain variable region
  • HCDR2 heavy chain variable region
  • LCVR light chain variable region
  • HCVR heavy chain variable region
  • HCDR2 HCDR2
  • HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 81
  • LCVR light chain variable region
  • said first antigen-binding domain that binds to a capsid of an AAV particle comprises :
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; 3) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 83, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 87; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
  • said first antigen-binding domain that binds to a capsid of an AAV particle comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1 159, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1 157;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 71
  • LCVR comprising the amino acid sequence of SEQ ID NO: 10
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 81
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • the molecule on the cell surface is asialoglycoprotein receptor 1 (ASGR1), transferrin receptor (TfR), or calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1).
  • ASGR1 asialoglycoprotein receptor 1
  • TfR transferrin receptor
  • CACNG1 calcium voltage-gated channel auxiliary subunit gamma 1
  • the molecule on the cell surface is ASGR1 .
  • the second antigen-binding domain that binds to ASGR1 comprises: a) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • said second antigen-binding domain that binds to ASGR1 comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 222, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 224, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 226; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 232, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 234, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 236; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:
  • said second antigen-binding domain that binds to ASGR1 comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • the molecule on the cell surface is TfR.
  • the second antigen-binding domain that binds to TfR comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 276;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 361 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 366;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 501 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 506;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 511 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 516; 24) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 521 , and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 526;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 531 , and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 536;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 557;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1119, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1127.
  • said second antigen-binding domain that binds to TfR comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 272, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 273, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 274; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 277, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 278, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 279;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 283, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 284, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 285; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 288, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 289, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 290;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 294, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 295, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 296; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 299, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 300, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 301 ;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 304, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 305, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 306; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 310, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 311 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 312;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 315, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 316, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 317; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 321 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 322, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 323;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 327
  • a HCDR2 comprising the amino acid sequence of SEQ ID NO: 328
  • a HCDR3 comprising the amino acid sequence of SEQ ID NO: 329
  • a LCDR1 comprising the amino acid sequence of SEQ ID NO: 333
  • a LCDR2 comprising the amino acid sequence of SEQ ID NO: 334
  • a LCDR3 comprising the amino acid sequence of SEQ ID NO: 335
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 339, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 340, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 341 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 345, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 347;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 351 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 352, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 353; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 357, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 358, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 359;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 362, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 363, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 364; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 367, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 368, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 369;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 373, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 374, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 375; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 378, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 379, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 380;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 383, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 384, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 385; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 388, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 389, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 390;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 394, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 395, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 396; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 400, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 401 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 402;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 405, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 406, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 407; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 410, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 411 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 412;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 415, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 416, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 417; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 420, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 421 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 422;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 426, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 427, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 428; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 432, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 433, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 434;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 437, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 438, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 439; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 442, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 443, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 444;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 448, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 449, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 450; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 453, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 454, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 455;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 458, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 459, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 460; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 463, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 464, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 465;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 469, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 470, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 471 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 475, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 476, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 477;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 481 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 482, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 483; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 486, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 487, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 488;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 492, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 493, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 494; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 497, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 498, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 499;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 507, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 508, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 509;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 517, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 518, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 519;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 522, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 523, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 524; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 527, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 528, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 529;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 537, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 538, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 539;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 543, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 544, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 545; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 548, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 549, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 550;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 558, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 559, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 560;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 563, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 564, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 565; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 568, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 569, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 570;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 573, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 574, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 575; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 578, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 579, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 580;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 583, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 584, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 585; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 588, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 589, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 590;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 594, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 595, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 596; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 600, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 601 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 602;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 605, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 606, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 607; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 611 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 612, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 613; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1121 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1123, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1125; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1129, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1131 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1133.
  • the second antigen-binding domain that binds to TfR comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 276
  • HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 361
  • LCVR comprising the amino acid sequence of SEQ ID NO: 366
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 501
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 506
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 511
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 516
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 521
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 526
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 531 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 536; 26) a HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 557;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 119, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1 127.
  • the molecule on the cell surface is CACNG1 .
  • the antigen-binding domain that binds to CACNG1 comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 803;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 823;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1181 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1189; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • the second antigen-binding domain that binds to CACNG1 comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 617, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 619, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 621 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 625, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 627, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 629;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 637, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 639, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 641 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 645, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 647, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 649;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 657, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 659, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 661 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 665, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 667, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 669;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 677, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 679, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 681 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 685, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 687, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 689;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 697, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 699, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 701 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 705, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 707, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 709;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 717, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 719, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 721 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 725, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 727, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 729;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 737, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 739, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 741 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 745, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 747, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 749;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 757, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 759, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 761 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 765, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 767, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 769;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 777, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 779, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 781 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 785, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 787, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 789;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 801 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 809;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 817, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 819, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 821 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 825, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 827, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 829;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 837, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 839, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 841 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 845, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 847, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 849;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 857, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 859, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 861 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 865, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 867, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 869;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 877, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 879, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 881 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 885, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 887, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 889;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 897, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 899, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 901 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 905, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 907, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 909;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 917, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 919, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 921 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 925, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 927, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 929;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 937, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 939, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 941 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 945, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 947, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 949; 18) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 957, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 959, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 961 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 965, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 967, and a LCDR3 comprising the amino acid sequence of SEQ
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1183, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1185, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1187; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1191 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1193, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1195; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1207, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1209, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1211 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1215, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1217, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1219.
  • the second antigen-binding domain that binds to CACNG1 comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 803; 1 1) a HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 823;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 181 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1189; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1”) operably linked to (ii) a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a first antigen-binding domain (“ABD1”); and c) a third polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); wherein ABD1 or ABD2 binds to a capsid of an adeno-associated virus (AAV) particle, and the other of ABD1 or ABD2 binds to
  • ABD1 binds to a capsid of an adeno-associated virus (AAV) particle and ABD2 binds to a molecule on the cell surface.
  • AAV adeno-associated virus
  • ABD2 binds to a capsid of an adeno-associated virus (AAV) particle and ABD1 binds to a molecule on the cell surface.
  • AAV adeno-associated virus
  • the first heavy chain region is linked to the second heavy chain region via a linker.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first scFv comprising a first antigen-binding domain (“ABD1”) operably linked to (ii) an Fc domain; b) a second polypeptide chain, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1 ”) operably linked to (ii) an Fc domain; and c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a second antigen-binding domain (“ABD2”); wherein ABD1 or ABD2 binds to a capsid of an adeno-associated virus (AAV) particle, and the other of ABD1 or ABD2 binds to
  • ABD1 binds to a capsid of an adeno-associated virus (AAV) particle and ABD2 binds to a molecule on the cell surface.
  • AAV adeno-associated virus
  • ABD2 binds to a capsid of an adeno-associated virus (AAV) particle and ABD1 binds to a molecule on the cell surface.
  • AAV adeno-associated virus
  • the first scFv and/or the first heavy chain region is linked to the Fc domain via a linker.
  • the ABD1 or ABD2 which binds to a capsid of an AAV particle comprises: a) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a heavy chain variable region (HCVR) that comprises a HCVR that comprises a HCVR
  • the ABD1 or ABD2 which binds to a capsid of an AAV particle comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO:
  • the ABD1 or ABD2 which binds to a capsid of an AAV particle comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; d) a HCVR comprising the amino acid sequence of SEQ ID NO: 42, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; e) a HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1 159, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10
  • the molecule on the cell surface is asialoglycoprotein receptor 1 (ASGR1), transferrin receptor (TfR), or calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1).
  • ASGR1 asialoglycoprotein receptor 1
  • TfR transferrin receptor
  • CACNG1 calcium voltage-gated channel auxiliary subunit gamma 1
  • the molecule on the cell surface is ASGR1 .
  • the other of ABD1 or ABD2 which binds to ASGR1 comprises: a) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • the other of ABD1 or ABD2 which binds to ASGR1 comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 222, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 224, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 226; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 232, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 234, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 236; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of
  • the other of ABD1 or ABD2 which binds to ASGR1 comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • the molecule on the cell surface is TfR.
  • the other of ABD1 or ABD2 which binds to TfR comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 276;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 361 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 366;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 501 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 506;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 511 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 516;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 521 , and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 526;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 531 , and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 536;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 557;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 11 19, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1127.
  • the other of ABD1 or ABD2 which binds to TfR comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 272, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 273, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 274; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 277, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 278, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 279;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 283, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 284, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 285; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 288, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 289, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 290;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 294, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 295, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 296; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 299, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 300, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 301 ;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 304, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 305, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 306; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 310, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 311 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 312;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 315, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 316, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 317; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 321 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 322, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 323;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 327
  • a HCDR2 comprising the amino acid sequence of SEQ ID NO: 328
  • a HCDR3 comprising the amino acid sequence of SEQ ID NO: 329
  • a LCDR1 comprising the amino acid sequence of SEQ ID NO: 333
  • a LCDR2 comprising the amino acid sequence of SEQ ID NO: 334
  • a LCDR3 comprising the amino acid sequence of SEQ ID NO: 335
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 339, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 340, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 341 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 345, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 347;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 351 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 352, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 353; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 357, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 358, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 359;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 362, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 363, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 364; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 367, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 368, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 369;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 373, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 374, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 375; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 378, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 379, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 380;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 383, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 384, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 385; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 388, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 389, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 390;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 394, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 395, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 396; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 400, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 401 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 402;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 405, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 406, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 407; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 410, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 411, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 412;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 415, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 416, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 417; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 420, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 421 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 422;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 426, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 427, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 428; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 432, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 433, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 434;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 437, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 438, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 439; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 442, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 443, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 444;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 448, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 449, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 450; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 453, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 454, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 455;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 458, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 459, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 460; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 463, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 464, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 465;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 469, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 470, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 471 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 475, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 476, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 477;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 481 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 482, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 483; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 486, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 487, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 488;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 492, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 493, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 494; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 497, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 498, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 499;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 507, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 508, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 509;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 517, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 518, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 519;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 522, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 523, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 524; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 527, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 528, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 529;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 537, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 538, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 539;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 543, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 544, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 545; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 548, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 549, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 550;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 558, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 559, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 560;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 563, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 564, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 565; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 568, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 569, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 570;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 573, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 574, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 575; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 578, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 579, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 580; 30) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 583, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 584, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 585; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 588, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 589, and a LCDR3 comprising the amino acid sequence of SEQ ID NO
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 594, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 595, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 596; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 600, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 601 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 602;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 605, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 606, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 607; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 611 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 612, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 613; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1121 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1123, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1125; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1129, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1131 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1133.
  • the other of ABD1 or ABD2 which binds to TfR comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 276
  • HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356; 9) a HCVR comprising the amino acid sequence of SEQ ID NO: 361 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 366;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 501
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 506
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 511
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 516
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 521
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 526
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 531
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 536
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 557;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 119, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1 127.
  • the molecule on the cell surface is CACNG1 .
  • the other of ABD1 or ABD2 which binds to CACNG1 comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 803;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 823;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1181 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1189; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • the other of ABD1 or ABD2 which binds to CACNG1 comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 617, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 619, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 621 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 625, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 627, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 629;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 637, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 639, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 641 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 645, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 647, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 649;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 657, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 659, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 661 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 665, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 667, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 669;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 677, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 679, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 681 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 685, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 687, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 689;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 697, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 699, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 701 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 705, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 707, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 709;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 717, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 719, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 721 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 725, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 727, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 729;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 737, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 739, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 741 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 745, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 747, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 749;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 757, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 759, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 761 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 765, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 767, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 769;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 777, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 779, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 781 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 785, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 787, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 789;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 801 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 809; 11) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 817, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 819, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 821 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 825, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 827, and a LCDR3 comprising the amino acid sequence of SEQ
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 837, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 839, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 841 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 845, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 847, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 849;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 857, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 859, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 861 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 865, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 867, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 869;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 877, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 879, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 881 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 885, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 887, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 889;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 897, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 899, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 901 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 905, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 907, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 909;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 917, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 919, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 921 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 925, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 927, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 929;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 937, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 939, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 941 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 945, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 947, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 949;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 957, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 959, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 961 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 965, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 967, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 969;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1183, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1185, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1187; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1191 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1193, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1195; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1207, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1209, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1211 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1215, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1217, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1219.
  • the other of ABD1 or ABD2 which binds to CACNG1 comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 803;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 823; 12) a HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 181 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1 189; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) an scFv comprising a first antigen-binding domain (“ABD1 ”) operably linked to (ii) a first heavy chain region of a first Fab (“Fab1”), said first heavy chain region operably linked to (iii) an Fc domain; b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a second heavy chain region of a second Fab (“Fab2”) operably linked to (ii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a second antigen-binding domain (“ABD2”); and d) a fourth polypeptide chain comprising a second light chain
  • two of ABD1 , ABD2 and ABD3 bind to a capsid of an AAV particle, and one of ABD1 , ABD2 and ABD3 binds to a molecule on a cell surface.
  • ABD2 and ABD3 bind to a capsid of an AAV particle, and ABD1 binds to a molecule on a cell surface.
  • ABD1 and ABD3 bind to a capsid of an AAV particle, and ABD2 binds to a molecule on a cell surface.
  • the scFv is linked to the first heavy chain region via a linker.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1 ”) operably linked to (ii) an Fc domain, said Fc domain operably linked to (iii) an scFv comprising a first antigen-binding domain (“ABD1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a second heavy chain region of a second Fab (“Fab2”) operably linked to (ii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a second antigen-binding domain (“ABD2”); and d) a fourth polypeptide chain comprising a second light chain that
  • two of ABD1 , ABD2 and ABD3 bind to a capsid of an AAV particle, and one of ABD1 , ABD2 and ABD3 binds to a molecule on a cell surface.
  • ABD2 and ABD3 bind to a capsid of an AAV particle, and ABD1 binds to a molecule on a cell surface.
  • ABD1 and ABD2 bind to a capsid of an AAV particle, and ABD3 binds to a molecule on a cell surface.
  • the scFv is linked to the Fc domain via a linker.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1”) operably linked to (ii) a second heavy chain region of a second Fab (“Fab2”), said second heavy chain region of Fab2 operably linked to (iii) an Fc domain; b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a third heavy chain region of a third Fab (“Fab3”) operably linked to (ii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a first antigen-binding domain (“ABD1 ”); d) a fourth polypeptide chain comprising a second light chain that pairs with
  • two of ABD1 , ABD2 and ABD3 bind to a capsid of an AAV particle, and one of ABD1 , ABD2 and ABD3 binds to a molecule on a cell surface.
  • ABD2 and ABD3 bind to a capsid of an AAV particle, and ABD1 binds to a molecule on a cell surface.
  • ABD1 and ABD3 bind to a capsid of an AAV particle, and ABD2 binds to a molecule on a cell surface.
  • the first heavy chain region is linked to the second heavy chain region via a linker.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1 ”) operably linked to (ii) an Fc domain, said Fc domain operably linked to (iii) a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a third heavy chain region of a third Fab (“Fab3”) operably linked to (ii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a first antigen-binding domain (“ABD1 ”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain
  • two of ABD1 , ABD2 and ABD3 bind to a capsid of an AAV particle, and one of ABD1 , ABD2 and ABD3 binds to a molecule on a cell surface.
  • ABD1 and ABD3 bind to a capsid of an AAV particle, and ABD2 binds to a molecule on a cell surface.
  • ABD1 and ABD2 bind to a capsid of an AAV particle, and ABD3 binds to a molecule on a cell surface.
  • the second heavy chain region is linked to the Fc domain via a linker.
  • a multispecific antibody, or a multispecific antigen-binding fragment thereof comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1”) operably linked to (ii) an scFv comprising a first antigen-binding domain (“ABD1 ”), said scFv operably linked to (iii) an Fc domain; b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a second heavy chain region of a second Fab (“Fab2”) operably linked to (ii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a second antigen
  • two of ABD1 , ABD2 and ABD3 bind to a capsid of an AAV particle, and one of ABD1 , ABD2 and ABD3 binds to a molecule on a cell surface.
  • ABD2 and ABD3 bind to a capsid of an AAV particle, and ABD1 binds to a molecule on a cell surface.
  • ABD1 and ABD2 bind to a capsid of an AAV particle, and ABD3 binds to a molecule on a cell surface.
  • the scFv is linked to the first heavy chain region via a linker.
  • a multispecific antibody, or a multispecific antigen-binding fragment thereof comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1 ”) operably linked to (ii) an Fc domain, said Fc domain operably linked to (iii) a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) an scFv comprising a first antigen-binding domain (“ABD1 ”) operably linked to (ii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a second antigen-binding domain
  • two of ABD1 , ABD2 and ABD3 bind to a capsid of an AAV particle, and one of ABD1 , ABD2 and ABD3 binds to a molecule on a cell surface.
  • ABD2 and ABD3 bind to a capsid of an AAV particle, and ABD1 binds to a molecule on a cell surface.
  • ABD1 and ABD2 bind to a capsid of an AAV particle, and ABD3 binds to a molecule on a cell surface.
  • the second heavy chain region is linked to the Fc domain via a linker.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1”) operably linked to (ii) a second heavy chain region of a second Fab (“Fab2”), said second heavy chain region operably linked to (iii) a third heavy chain region of a third Fab (“Fab3”); b) a second polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a first antigen-binding domain (“ABD1”); and c) a third polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); d) a fourth polypeptide chain comprising a third light chain
  • two of ABD1 , ABD2 and ABD3 bind to a capsid of an AAV particle, and one of ABD1 , ABD2 and ABD3 binds to a molecule on a cell surface.
  • ABD2 and ABD3 bind to a capsid of an AAV particle, and ABD1 binds to a molecule on a cell surface.
  • ABD1 and ABD3 bind to a capsid of an AAV particle, and ABD2 binds to a molecule on a cell surface.
  • the first heavy chain region is operably linked to the second heavy chain region and/or the second heavy chain region is operably linked to the third heavy chain region via a linker.
  • the at least one of ABD1 , ABD2 and ABD3 which binds to a capsid of an AAV particle comprises: a) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a heavy chain variable region (HCVR) that comprises a
  • the at least one of ABD1 , ABD2 and ABD3 which binds to a capsid of an AAV particle comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the
  • the at least one of ABD1 , ABD2 and ABD3 which binds to a capsid of an AAV particle comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; d) a HCVR comprising the amino acid sequence of SEQ ID NO: 42, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; e) a HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1159, and/or a LCVR comprising the amino acid
  • said molecule on the cell surface is asialoglycoprotein receptor 1 (ASGR1), transferrin receptor (TfR), or calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1).
  • ASGR1 asialoglycoprotein receptor 1
  • TfR transferrin receptor
  • CACNG1 calcium voltage-gated channel auxiliary subunit gamma 1
  • said molecule on the cell surface is ASGR1.
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to ASGR1 comprises: a) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to ASGR1 comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 222, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 224, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 226; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 232, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 234, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 236; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to ASGR1 comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • the molecule on the cell surface is TfR.
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to TfR comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 276;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 361 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 366;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 501 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 506;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 511 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 516;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 521 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 526;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 531 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 536;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 557; 28) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVRthat comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 11 19, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1127.
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to TfR comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 272, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 273, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 274; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 277, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 278, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 279;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 283, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 284, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 285; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 288, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 289, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 290;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 294, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 295, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 296; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 299, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 300, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 301 ;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 304, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 305, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 306; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 310, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 311 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 312;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 315, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 316, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 317; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 321 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 322, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 323;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 327
  • a HCDR2 comprising the amino acid sequence of SEQ ID NO: 328
  • a HCDR3 comprising the amino acid sequence of SEQ ID NO: 329
  • a LCDR1 comprising the amino acid sequence of SEQ ID NO: 333
  • a LCDR2 comprising the amino acid sequence of SEQ ID NO: 334
  • a LCDR3 comprising the amino acid sequence of SEQ ID NO: 335
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 339, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 340, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 341 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 345, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 347;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 351 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 352, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 353; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 357, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 358, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 359;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 362, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 363, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 364; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 367, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 368, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 369;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 373, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 374, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 375; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 378, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 379, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 380;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 383, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 384, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 385; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 388, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 389, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 390;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 394, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 395, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 396; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 400, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 401 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 402;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 405, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 406, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 407; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 410, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 411 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 412;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 415, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 416, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 417; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 420, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 421 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 422;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 426, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 427, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 428; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 432, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 433, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 434;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 437, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 438, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 439; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 442, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 443, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 444;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 448, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 449, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 450; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 453, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 454, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 455; 18) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 458, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 459, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 460; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 463, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 464, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 4
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 469, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 470, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 471 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 475, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 476, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 477;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 481 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 482, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 483; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 486, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 487, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 488;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 492, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 493, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 494; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 497, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 498, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 499;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 507, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 508, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 509;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 517, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 518, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 519;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 522, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 523, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 524; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 527, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 528, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 529;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 537, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 538, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 539;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 543, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 544, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 545; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 548, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 549, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 550;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 558, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 559, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 560;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 563, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 564, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 565; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 568, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 569, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 570;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 573, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 574, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 575; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 578, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 579, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 580;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 583, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 584, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 585; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 588, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 589, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 590;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 594, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 595, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 596; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 600, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 601 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 602;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 605, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 606, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 607; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 611 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 612, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 613; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1121 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1123, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1125; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1129, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1 131 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1133.
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to TfR comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 276
  • HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 361
  • LCVR comprising the amino acid sequence of SEQ ID NO: 366
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 501
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 506
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 51 1
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 516
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 521
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 526
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 531
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 536
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 557;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 119, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1 127.
  • the molecule on the cell surface is CACNG1 .
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to CACNG1 comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 803;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 823;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1181 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1189; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to CACNG1 comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 617, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 619, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 621 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 625, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 627, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 629;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 637, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 639, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 641 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 645, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 647, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 649;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 657, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 659, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 661 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 665, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 667, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 669;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 677, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 679, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 681 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 685, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 687, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 689;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 697, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 699, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 701 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 705, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 707, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 709;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 717, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 719, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 721 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 725, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 727, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 729;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 737, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 739, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 741 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 745, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 747, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 749;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 757, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 759, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 761 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 765, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 767, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 769;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 777, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 779, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 781 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 785, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 787, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 789;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 801 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 809;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 817, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 819, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 821 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 825, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 827, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 829;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 837, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 839, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 841 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 845, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 847, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 849;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 857, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 859, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 861 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 865, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 867, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 869;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 877, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 879, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 881 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 885, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 887, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 889;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 897, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 899, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 901 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 905, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 907, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 909;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 917, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 919, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 921 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 925, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 927, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 929;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 937, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 939, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 941 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 945, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 947, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 949;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 957, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 959, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 961 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 965, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 967, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 969;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1 183, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1185, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1187; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1191 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1 193, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1195; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1207, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1209, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 121 1 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1215, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1217, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1219.
  • the other(s) of ABD1 , ABD2 and ABD3 which binds to
  • CACNG1 comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 803;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 823;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 181 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1 189; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first scFv comprising a first antigen-binding domain (“ABD1 ”) operably linked to (ii) a first heavy chain region of a first Fab (“Fab1 ”), said first heavy chain region of Fab1 operably linked to (iii) an Fc domain; b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a second scFv comprising a second antigen-binding domain (“ABD2”) operably linked to (ii) a second heavy chain region of a second Fab (“Fab2”), said second heavy chain region of Fab2 operably linked to (iii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the
  • two of ABD1 , ABD2, ABD3, and ABD4 bind to a capsid of an AAV particle, and two of ABD1 , ABD2, ABD3 and ABD4 binds to a molecule on a cell surface.
  • ABD1 and ABD2 bind to a capsid of an AAV particle, and ABD3 and ABD4 binds to a molecule on a cell surface.
  • ABD3 and ABD4 bind to a capsid of an AAV particle, and ABD1 and ABD2 binds to a molecule on a cell surface.
  • the first scFv is linked to the first heavy chain region and/or the second scFv is linked to the second heavy chain region via a linker.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1 ’’) operably linked to (ii) an Fc domain, said Fc domain operably linked to (iii) a first scFv comprising a first antigen-binding domain (“ABD1 ”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a second heavy chain region of a second Fab (“Fab2”) operably linked to (ii) an Fc domain, said Fc domain operably linked to (iii) a second scFv comprising a second antigen-binding domain (“ABD2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab
  • two of ABD1 , ABD2, ABD3, and ABD4 bind to a capsid of an AAV particle, and two of ABD1 , ABD2, ABD3 and ABD4 binds to a molecule on a cell surface.
  • ABD1 and ABD2 bind to a capsid of an AAV particle, and ABD3 and ABD4 binds to a molecule on a cell surface.
  • ABD3 and ABD4 bind to a capsid of an AAV particle, and ABD1 and ABD2 binds to a molecule on a cell surface.
  • the first scFv and/or second scFv is linked to the Fc domain via a linker.
  • a multispecific antibody or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation, (i) a first heavy chain region of a first Fab (“Fab1”) operably linked to (ii) a second heavy chain region of a second Fab (“Fab2”) operably linked to (iii) an Fc domain; b) a second polypeptide chain comprising, in an N- to C-terminal orientation, (i) a third heavy chain region of a third Fab (“Fab3) operable liked to (ii) a fourth heavy chain region of a fourth Fab (“Fab4”) operably linked to (iii) an Fc domain; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1 , wherein Fab1 comprises a first antigen-binding domain (“ABD1 ”); d) a fourth antigen-binding domain
  • two of ABD1 , ABD2, ABD3, and ABD4 bind to a capsid of an AAV particle, and two of ABD1 , ABD2, ABD3 and ABD4 binds to a molecule on a cell surface.
  • ABD1 and ABD3 bind to a capsid of an AAV particle, and ABD2 and ABD4 binds to a molecule on a cell surface.
  • ABD2 and ABD4 bind to a capsid of an AAV particle, and ABD1 and ABD3 binds to a molecule on a cell surface.
  • the first heavy chain region is linked to the second heavy chain region and/or the third heavy chain region is linked to fourth heavy chain region via a linker.
  • the at least one of ABD1 , ABD2, ABD3, and ABD4 which binds to a capsid of an AAV particle comprises: a) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (HCVR) that comprises a HCDR1 , HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a light chain variable region (LCVR) that comprises a LCDR1 , LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a heavy chain variable region (HCVR) that comprises
  • the at least one of ABD1 , ABD2, ABD3, and ABD4 which binds to a capsid of an AAV particle comprises: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2
  • the at least one of ABD1 , ABD2, ABD3, and ABD4 which binds to a capsid of an AAV particle comprises: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 2, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a HCVR comprising the amino acid sequence of SEQ ID NO: 22, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; d) a HCVR comprising the amino acid sequence of SEQ ID NO: 42, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; e) a HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1159, and/or a LCVR comprising
  • said molecule on the cell surface is asialoglycoprotein receptor 1 (ASGR1), transferrin receptor (TfR), or calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1).
  • ASGR1 asialoglycoprotein receptor 1
  • TfR transferrin receptor
  • CACNG1 calcium voltage-gated channel auxiliary subunit gamma 1
  • said molecule on the cell surface is ASGR1 .
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to ASGR1 comprises: a) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to ASGR1 comprises a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 222, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 224, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 226; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 232, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 234, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 236; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to ASGR1 comprises a) a HCVR comprising the amino acid sequence of SEQ ID NO: 220 or 1239, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; or b) a HCVR comprising the amino acid sequence of SEQ ID NO: 230, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 10.
  • said molecule on the cell surface is TfR.
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to TfR comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 276;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 361 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 366;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 501 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 506;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 511 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 516;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 521 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 526; 25) a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 531 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 536;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 557;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1119, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1127.
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to TfR comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 272, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 273, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 274; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 277, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 278, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 279;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 283, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 284, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 285; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 288, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 289, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 290;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 294, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 295, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 296; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 299, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 300, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 301 ;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 304, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 305, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 306; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 310, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 311 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 312;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 315, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 316, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 317; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 321 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 322, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 323;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 327
  • a HCDR2 comprising the amino acid sequence of SEQ ID NO: 328
  • a HCDR3 comprising the amino acid sequence of SEQ ID NO: 329
  • a LCDR1 comprising the amino acid sequence of SEQ ID NO: 333
  • a LCDR2 comprising the amino acid sequence of SEQ ID NO: 334
  • a LCDR3 comprising the amino acid sequence of SEQ ID NO: 335
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 339, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 340, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 341 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 345, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 346, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 347;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 351 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 352, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 353; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 357, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 358, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 359;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 362, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 363, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 364; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 367, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 368, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 369;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 373, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 374, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 375; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 378, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 379, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 380;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 383, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 384, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 385; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 388, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 389, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 390;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 394, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 395, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 396; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 400, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 401 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 402;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 405, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 406, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 407; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 410, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 411 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 412;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 415, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 416, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 417; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 420, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 421 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 422;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 426, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 427, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 428; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 432, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 433, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 434;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 437, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 438, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 439; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 442, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 443, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 444;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 448, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 449, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 450; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 453, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 454, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 455;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 458, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 459, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 460; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 463, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 464, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 465;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 469, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 470, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 471 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 475, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 476, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 477;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 481 , a HCDR2 comprising the amino acid sequence of SEQ ID NO: 482, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 483; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 486, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 487, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 488;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 492, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 493, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 494; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 497, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 498, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 499;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 507, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 508, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 509; 23) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 517, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 518, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 5
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 522, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 523, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 524; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 527, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 528, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 529;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 537, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 538, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 539;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 543, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 544, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 545; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 548, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 549, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 550;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 558, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 559, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 560;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 563, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 564, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 565; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 568, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 569, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 570;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 573, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 574, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 575; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 578, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 579, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 580;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 583, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 584, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 585; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 588, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 589, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 590;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 594, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 595, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 596; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 600, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 601 , and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 602;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 605, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 606, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 607; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 61 1 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 612, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 613; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1 121
  • a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1123
  • a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1125
  • a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1129
  • a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1 131
  • a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1133.
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to TfR comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 270 or 271
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 276
  • HCVR comprising the amino acid sequence of SEQ ID NO: 281 or 282, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 287;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 292 or 293, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 298;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 303, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 308 or 309;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 314, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 319 or 320;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 325 or 326, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 331 or 332;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 337 or 338, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 343 or 344;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 349 or 350, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 355 or 356;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 361
  • LCVR comprising the amino acid sequence of SEQ ID NO: 366
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 371 or 372, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 377;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 382, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 387;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 392 or 393, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 398 or 399;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 404, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 409;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 414, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 419;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 424 or 425, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 430 or 431;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 436, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 441 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 446 or 447, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 452;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 457, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 462;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 467 or 468, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 473 or 474;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 479 or 480, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 485;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 490 or 491 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 496;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 501
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 506
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 511
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 516
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 521
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 526
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 531
  • a LCVR comprising the amino acid sequence of SEQ ID NO: 536
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 541 or 542, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 547;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 552, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 557; 28) a HCVR comprising the amino acid sequence of SEQ ID NO: 562, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 567;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 572, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 577;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 582, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 587;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 592 or 593, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 598 or 599 ;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 604, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 609 or 610; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 119, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1 127.
  • said molecule on the cell surface is CACNG1 .
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to CACNG1 comprises:
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 803;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 823;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1181 , and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1189; or
  • a HCVR that comprises the HCDR1 , HCDR2 and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR that comprises the LCDR1 , LCDR2 and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to CACNG1 comprises:
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 617, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 619, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 621 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 625, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 627, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 629;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 637, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 639, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 641 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 645, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 647, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 649;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 657, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 659, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 661 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 665, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 667, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 669;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 677, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 679, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 681 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 685, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 687, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 689;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 697, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 699, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 701 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 705, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 707, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 709;
  • HCDR1 comprising the amino acid sequence of SEQ ID NO: 717, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 719, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 721 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 725, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 727, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 729;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 737, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 739, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 741 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 745, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 747, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 749;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 757, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 759, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 761 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 765, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 767, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 769;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 777, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 779, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 781 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 785, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 787, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 789;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 801 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 809;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 817, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 819, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 821 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 825, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 827, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 829;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 837, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 839, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 841 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 845, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 847, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 849;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 857, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 859, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 861 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 865, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 867, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 869;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 877, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 879, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 881 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 885, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 887, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 889;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 897, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 899, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 901 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 905, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 907, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 909;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 917, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 919, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 921 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 925, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 927, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 929;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 937, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 939, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 941 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 945, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 947, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 949;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 957, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 959, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 961 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 965, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 967, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 969;
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1 183, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1185, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 1187; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1191 , a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1 193, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1195; or
  • a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1207, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 1209, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 121 1 ; and/or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1215, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 1217, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 1219.
  • the other(s) of ABD1 , ABD2, ABD3, and ABD4 which binds to CACNG1 comprises:
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 615, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 623;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 635, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 643;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 655, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 663;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 675, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 683;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 695, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 703;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 715, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 723;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 735, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 743;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 755, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 763;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 775, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 783;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 795, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 803;
  • HCVR comprising the amino acid sequence of SEQ ID NO: 815, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 823;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 835, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 843;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 855, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 863;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 875, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 883;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 895, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 903;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 915, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 923;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 935, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 943;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 955, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 963;
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1 181 , and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1 189; or
  • a HCVR comprising the amino acid sequence of SEQ ID NO: 1205, and/or a LCVR comprising the amino acid sequence of SEQ ID NO: 1213.
  • the linker is:
  • the linker is:
  • the linker is:
  • the linker is:
  • the linker is 5 amino acids to 25 amino acids in length.
  • the linker is 10 amino acids to 60 amino acids in length.
  • the linker is 20 amino acids to 50 amino acids in length.
  • the linker is 25 to 35 amino acids in length.
  • the linker is or comprises a multimer of G n S (SEQ ID NO:
  • n is an integer from 1 to 10.
  • the linker is or comprises a multimer of G 4 S (SEQ ID NO: 242).
  • the linker is or comprises two consecutive glycines (2Gly), three consecutive glycines (3Gly), four consecutive glycines (4Gly (SEQ ID NO: 243)), five consecutive glycines (5Gly (SEQ ID NO: 244)), six consecutive glycines (6Gly (SEQ ID NO: 245)), seven consecutive glycines (7Gly (SEQ ID NO: 246)), eight consecutive glycines (8Gly (SEQ ID NO: 247)) or nine consecutive glycines (9Gly (SEQ ID NO: 248)).
  • one or more light chains are universal light chains.
  • a light chain constant region (CL) and a first heavy chain constant region (CH1) of one or more Fabs are in a CrossmAb arrangement.
  • the multispecific antibodies or multispecific antigenbinding fragments comprise an Fc heterodimer.
  • the Fc domains in the Fc heterodimer comprise knob-in-hole mutations as compared to a wild-type Fc domain.
  • one Fc domain in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild-type Fc domain
  • the other Fc domain in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild-type Fc domain.
  • At least one Fc domain in the Fc heterodimer comprises a star mutation as compared to a wild-type Fc domain.
  • one Fc domain in the Fc heterodimer comprises amino acid mutations H435R and/or Y436F (according to EU numbering) as compared to a wild-type Fc domain.
  • said capsid comprises one or more wild-type AAV capsid polypeptides.
  • said capsid comprises one or more non-wild-type AAV capsid polypeptides.
  • the multispecific antibodies or multispecific antigen-binding fragments can be a bispecific antibody or bispecific antigen-binding fragment thereof.
  • composition comprising a multispecific antibody or multispecific antigen-binding fragment described herein, and a pharmaceutically acceptable carrier or excipient.
  • a molecular complex comprising an AAV particle bound to one or more antibodies and/or antigen-binding fragments described herein.
  • said AAV particle comprises one or more mutations in one or more AAV capsid proteins inhibiting the natural tropism of said AAV particle.
  • composition comprising a molecular complex described herein and a pharmaceutically acceptable carrier or excipient.
  • a method of preparing the molecular complex described herein comprising incubating said AAV particle in the presence of said one or more antibodies and/or antigen-binding fragments under conditions allowing specific binding of said one or more antibodies and/or antigen-binding fragments to said AAV particle capsid.
  • a molecular complex comprising an AAV particle bound to one or more multispecific antibodies and/or multispecific antigen-binding fragments described herein.
  • said AAV particle comprises one or more mutations in one or more AAV capsid proteins inhibiting the natural tropism of said AAV particle.
  • composition comprising a molecular complex described herein and a pharmaceutically acceptable carrier or excipient.
  • a method of preparing a molecular complex described herein comprising incubating said AAV particle in the presence of said one or more multispecific antibodies and/or multispecific antigen-binding fragments under conditions allowing specific binding of said one or more multispecific antibodies and/or multispecific antigen-binding fragments to said AAV particle capsid.
  • a method for targeting an AAV particle to a cell expressing a molecule on the cell surface comprising contacting the cell with a molecular complex described herein or a pharmaceutical composition described herein, wherein said molecular complex comprises one or more multispecific antibodies and/or multispecific antigen-binding fragments which bind to said molecule on the cell surface.
  • a method for delivering a polynucleotide to a cell expressing a molecule on the cell surface comprising contacting the cell with a molecular complex described herein or a pharmaceutical composition described herein, wherein said molecular complex comprises the AAV particle comprising said polynucleotide and bound to one or more multispecific antibodies and/or multispecific antigen-binding fragments which bind to said molecule on the cell surface.
  • said cell is in a subject and said molecular complex is administered to the subject.
  • said AAV particle does not target said cell in the absence of said one or more multispecific antibodies and/or multispecific antigen-binding fragments.
  • any of the features or components of embodiments discussed above or herein may be combined, and such combinations are encompassed within the scope of the present disclosure. Any specific value discussed above or herein may be combined with another related value discussed above or herein to recite a range with the values representing the upper and lower ends of the range, and such ranges are encompassed within the scope of the present disclosure.
  • Figures 1A-1L depict graphs of binding activities of the anti-adeno-associated virus (AAV) antibodies described herein to various adeno-associated virus (AAV) serotypes. RLU, relative light units.
  • Figures 2A-2J depict graphs showing immunoglobulin gamma Fc receptor I (FcGR- 1) AAV retargeting by anti-AAV antibodies derived using next-generation sequencing (NGS)Zmass spectrometry (MS) methods ( Figures 2A-2F) and by anti-AAV antibodies derived from hybridoma ( Figures 2G-2J) described herein for various AAV serotypes.
  • FcGR- 1 immunoglobulin gamma Fc receptor I
  • NGS next-generation sequencing
  • MS mass spectrometry
  • FIG 3 shows a schematic representation of alternative format antibody designs for bispecific antibodies of the present disclosure.
  • Exemplary bispecific antibodies target AAV and Asialoglycoprotein Receptor 1 (ASGR1).
  • Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle (e.g., ⁇ ).
  • Figure 4 displays a description of alternative format bispecific antibody molecules described herein.
  • Figure 5 illustrates an example rationale for anti-AAV antibody selection.
  • Figures 6A-6J depict graphs of binding affinities of alternative format antibodies described herein (e.g., anti-AAV-ASGR1 bispecific antibodies) to an AAV2 heparin binding mutant (HBM) serotype.
  • the AAV2-HBM serotype contains R585A R588A mutations. RLU, relative light units.
  • FIGs 7A-7B illustrate that bispecific antibodies can effectively retarget adeno- associated virus (AAV) to the central nervous system (CNS).
  • a schematic representation of anti-transferrin receptor (TfR) x anti-AAV bispecific antibody retargeting of AAV to the CNS is depicted in Figure 7A.
  • a comparison of wild-type (WT) AAV9, covalent-platform control and bispecific platform retargeting of AAV to cerebellum, cortex, and hippocampus is shown in Figure 7B.
  • BBB blood-brain barrier.
  • FIGs 8A-8B demonstrate that liver detargeting can be controlled by modulating antibody concentration [Ab] and/or use of a detargeting capsid.
  • a comparison of transduction efficiency between the covalent platform and the bispecific platform evaluated using cDNA quantitation is shown in Figure 8A.
  • a comparison between detargeted AAV9 and WT AA9 using the bispecific platform in cerebellum and liver is shown in Figure 8B.
  • IHC immunohistochemistry.
  • FIG. 9 shows a schematic representation of AAV x CACNG1 alternative format (AF) antibodies AF70 and AF71.
  • AF70 comprises anti-AAV#70 scFv fused to the N-terminus of anti-CACNG1 REGN10717 hlgG1 N297G antibody.
  • AF71 comprises anti-AAV#70 scFv fused to the C-terminus of anti-CACNG1 REGN10717 hlgG1 N297G antibody. Disulfide bonds are indicated by S-S.
  • FIG. 10 shows flow cytometry data illustrating co-incubation of AAV9 W503A with AF70 (top two rows) and AF71 (bottom two rows) resulted in improved transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing mouse CACNG1 (mCACNGI). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1 :1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1 :9) as assessed by percent (%) GFP positive cells.
  • FIG 11 depicts line graphs showing co-incubation of AAV9 W503A with AF70 (top) and AF71 (bottom) resulted in improved transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing mouse CACNG1 (mCACNGI). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1 :1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1 :9) as assessed by mean fluorescence intensity (MFI).
  • MFI mean fluorescence intensity
  • FIG. 12 shows flow cytometry data illustrating co-incubation of AAV9 W503A with AF70 (top two rows) and AF71 (bottom two rows) resulted in improved AAV transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing human CACNG1 (hCACNGI). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1 :1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1 :9) as assessed by percent (%) GFP positive cells.
  • Figure 13 depicts line graphs showing co-incubation of AAV9 W503A with AF70 (top) and AF71 (bottom) resulted in improved AAV transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing human CACNG1 (hCACNGI). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1 :1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1 :9) as assessed by mean fluorescence intensity (MFI).
  • MFI mean fluorescence intensity
  • Figure 14 shows immunohistochemical staining of differentiated C2C12 myotubes for Myosin Heavy Chain (MyHC) and demonstration that incubation of AAV with AF70 and AF71 enhanced transduction into the myotubes as determined by GFP fluorescence.
  • MyHC Myosin Heavy Chain
  • Figure 15 shows immunohistochemical staining of differentiated human myotubes for Myosin Heavy Chain (MyHC) and demonstration that incubation of AAV with AF70 and AF71 enhanced transduction into the myotubes as determined by GFP fluorescence.
  • Human myotubes were most efficiently transduced with AAV complexed with AF71 at molar ratio 1 :3 and 1 :9.
  • Figures 16A-16D demonstrate incubation of AAV with AF70 and AF71 enhanced transduction into differentiated C2C12 myotubes as determined by quantification of GFP positive cells.
  • Figures 17A-17D demonstrate incubation of AAV with AF70 and AF71 enhanced transduction into differentiated human myotubes as determined by quantification of GFP positive cells.
  • Figures 18A-18B show non-limiting examples of AAVx mTfR alternative format (AF) antibodies described herein.
  • Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle (e.g., ⁇ ).
  • Figure 19 shows an example experimental setup used to test alternative format antibodies binding to AAV9W503A virus by ELISA.
  • Figure 20 depicts ELISA data for AAV x mTfR alternative format antibodies binding to AAV9W503A.
  • Figure 21 shows a schematic diagram of a FLuc assay protocol used to test retargeting of AAV9W503A using mTfR alternative format antibodies on 293T cells expressing mTfR receptor.
  • Figure 22 shows a line graph of data generated in experiments testing AAV9W503A retargeting using AAVxmTfR alternative format antibodies on mTfR293T cells.
  • Figures 23A-23C illustrate a retargeting assay using AAV9 scCBH.eGFP.
  • Figures 24A-24B show in vitro test infection results for in vivo injection samples.
  • Figures 25A-25F depict AAV x mTfR liver and brain (hippocampus, cortex, and cerebellum) green fluorescent protein (GFP) staining for control groups (Figure 25A) and alternative format designs, AAV x mTfR AF1 (Figure 25B), AAV x mTfR AF3 ( Figure 25C), AAV x mTfR AF5 ( Figure 25D), AAV x mTfR AF7 ( Figure 25E), and AAV x mTfR AF9 ( Figure 25F).
  • GFP green fluorescent protein
  • Figure 26 shows relative RNA expression of GFP in liver samples as determined by RT-qPCR.
  • Figure 27 shows RNA expression of GFP in brain samples as determined by RT- qPCR.
  • Figures 28A-28D depict GFP staining in brain, heart and liver tissues from mice receiving AAV9 ( Figures 28A-28B) or AAV9W503A ( Figures 28C and 28D) complexed with AAV x mTfR alternative format AF7 at AAV vector genome (VG) to antibody (Ab) ratios (VG:Ab ratios) of 1 :9 and 1 :3.
  • AAV9 Figures 28A-28B
  • AAV9W503A Figures 28C and 28D
  • Figures 29A-29I depict AAV x mTfR alternative format designs AF3 and AF7.
  • Figure 29A provides a description of AAV x mTfR alternative format designs AF3 and AF7.
  • Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle (e.g., ⁇ ).
  • Figures 29B-29E show examples of AAV x mTfR AF3 amino acid sequences ( Figure 29B) and corresponding nucleotide sequences ( Figures 29C-29E).
  • Figures 29F-29I show examples of AAV x mTfR AF7 amino acid sequences (Figure 29F) and corresponding nucleotide sequences ( Figures 29G-29I).
  • Figures 30A-30G depict AAV x CACNGI alternative format designs AF70 and AF71.
  • Figure 30A provides a description of AAV x CACNG1 alternative format designs AF70 and AF71.
  • Figures 30B-30G show examples of AAV x mTfR AF70 amino acid sequences (Figure 30B) and corresponding nucleotide sequences ( Figures 30C-30D).
  • Figures 30E-30G show examples of AAV x mTfR AF71 amino acid sequences ( Figure 30E) and corresponding nucleotide sequences (Figures 30F-30G).
  • Figure 31 illustrates AAV x CACNG1 bispecific antibody enhancement of transduction into CACNG1 overexpressing 293 cells. GFP expression was assessed by flow cytometry and is shown as % GFP positive cells (top panels) or MFI of GFP expressing cells (bottom panels).
  • Figure 32 depicts an example of a study design for testing Hu37 complexed with anti-AAV x CACNG1 2x2 antibodies in D2.MDX mice.
  • Figure 33 shows in vitro transduction in HEK293-hCACNG1 of complexes prepared for in vivo study.
  • Figures 34A-34C illustrate improved Hu37 transduction in muscle tissues when complexed with an 2x2 anti-CACNG1xAAV alternative format antibody.
  • Figures 35A-35B illustrate bispecific antibody enhancement of Hu37 transduction into skeletal muscle.
  • Figures 36A-36B depict AAV x ASGR alternative format designs AF21 (REGN16199), AF22 (REGN16200), AF29, AF30 (REGN16204), AF32 (REGN16202), AF37, AF41 , AF60A, AF61A, AF62, and AF63.
  • Figure 36A provides a description of AAV x ASGR alternative format designs AF21 (REGN16199), AF22 (REGN16200), AF29, AF30 (REGN16204), and AF32 (REGN16202).
  • Figure 36B provides a description of AAV x ASGR alternative format designs AF37, AF41 , AF60A, AF61A, AF62, and AF63.
  • Figure discloses “3xG4S” as SEQ ID NO: 1115 and “4xG4S” as SEQ ID NO: 1161.
  • Figures 37A-37B depict IVIS (In Vivo Imaging Instrument, Perkin Elmer) data illustrating retargeting of AAV to liver with AF30 and AF32.
  • Figure 38 depicts IVIS data that demonstrate retargeting of multiple serotypes to liver with AF30.
  • Figures 39A-39D depict IVIS & PK qPCR data that demonstrate retargeting to liver with antibodies comprised of either one or two anti-AAV binding arms.
  • Figures 40A-40C depict IVIS, PK qPCR, & ELISA data that demonstrate antibody can effectively retarget AAV when dosed prior to AAV administration.
  • Figures 41A-41B depict IVIS & PK qPCR data that demonstrate retargeting of REGN16199 with and without Fc.
  • Figures 42A-42F depict IVIS, PK qPCR, & RNA Taqman data that demonstrate successful targeting with linear Fab formats.
  • Figure 43 depicts PK qPCR data of serum samples 24 hours after administration of various antibody formats complexed with AAV.
  • Figure 44 depicts IVIS data that demonstrate retargeting of AAV with a variety of different antibody formats.
  • Figure 45 depicts IVIS data that demonstrate retargeting of AAV with antibody comprised of one anti-AAV arm and one anti-ASGR1 arm.
  • Figures 46A-46I depict AAV x ASGR alternative format designs AF1 , AF5, and AF9.
  • Figures 46A-46C show examples of AAV x ASGR AF1 amino acid sequences ( Figure 46A) and corresponding nucleotide sequences ( Figures 46B-46C).
  • Figures 46D-46F show examples of AAV x ASGR AF5 amino acid sequences ( Figure 46D) and corresponding nucleotide sequences ( Figures 46E-46F).
  • Figures 46G-46I show examples of AAV x ASGR AF9 amino acid sequences (Figure 46G) and corresponding nucleotide sequences ( Figures 46H-46I).
  • Figures 47A-47I depict AAV x mTfR alternative format designs AF1 , AF5, and AF9.
  • Figures 47A-47C show examples of AAV x mTfR AF1 amino acid sequences ( Figure 47A) and corresponding nucleotide sequences ( Figures 47B-47C).
  • Figures 47D-47F show examples of AAV x mTfR AF5 amino acid sequences ( Figure 47D) and corresponding nucleotide sequences ( Figures 47E-47F).
  • Figures 47G-47I show examples of AAV x mTfR AF9 amino acid sequences (Figure 47G) and corresponding nucleotide sequences ( Figures 47H-47I).
  • Figure discloses “3xG4S” as SEQ ID NO: 1115 and “4xG4S” as SEQ ID NO: 1161.
  • antigen encompasses any agent (e.g., protein, peptide, polysaccharide, glycoprotein, glycolipid, nucleotide, portions thereof, or combinations thereof) that, when introduced into an immunocompetent host is recognized by the immune system of the host and is capable of eliciting an immune response by the host.
  • agent e.g., protein, peptide, polysaccharide, glycoprotein, glycolipid, nucleotide, portions thereof, or combinations thereof
  • epitope can refer to an antigenic determinant that interacts with a specific antigen-binding site in the variable region of an antibody molecule known as a paratope.
  • a single antigen may have more than one epitope.
  • different antibodies may bind to different areas on an antigen and may have different biological effects.
  • Epitopes may be either conformational or linear.
  • a conformational epitope is produced by spatially juxtaposed amino acids from different segments of the linear polypeptide chain.
  • a linear epitope is one produced by adjacent amino acid residues in a polypeptide chain.
  • an epitope may include moieties of saccharides, phosphoryl groups, or sulfonyl groups on the antigen.
  • Epitopes may also be defined as structural or functional. Functional epitopes are generally a subset of structural epitopes and are defined as those residues that directly contribute to the affinity of the interaction between a major histocompatibility complex (MHC) molecule and the antigen.
  • MHC major histocompatibility complex
  • antigen-binding molecule refers in its broadest sense to a molecule that specifically binds to an antigen.
  • an antigen-binding molecule is an antibody or an antigen-binding fragment of an antibody, including, e.g., multispecific antibodies such as bispecific antibodies or fragments thereof.
  • multispecific antigen-binding molecule or “multispecific binding molecule” or “MBM” includes molecules (e.g., antibodies and antigen-binding fragments of antibodies) that bind two or more (e.g., three or four) different epitopes or antigens.
  • the multispecific antigen-binding molecules are bispecific (e.g., bispecific antibodies).
  • the multispecific antigen-binding molecules are trispecific.
  • the multispecific antigen-binding molecules are tetraspecific.
  • the present disclosure includes multispecific (e.g., bispecific) antigen-binding molecules (e.g., antibodies) that specifically bind a capsid of an AAV particle and a molecule of a cell surface.
  • antigen-binding molecules may be referred to herein as, e.g., “anti- AAV x anti-cell surface molecule” or other similar terminology (e.g., anti-AAV/anti-cell surface molecule).
  • a multispecific antigen-binding molecule of the disclosure may comprise a first ABD (“ABD1”), a second ABD (“ABD2”), a third ABD (“ABD3”), and/or a fourth ABD (“ABD4”), each of which may be part of, e.g., an scFv or a Fab.
  • antibody means any antigen-binding molecule or molecular complex comprising at least one complementarity determining region (CDR) that specifically binds to or interacts with a particular antigen.
  • CDR complementarity determining region
  • antibody includes immunoglobulin molecules comprising four polypeptide chains, two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, as well as multimers thereof (e.g., IgM).
  • IgM multimers thereof
  • antibody also includes immunoglobulin molecules consisting of four polypeptide chains, two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds.
  • Each heavy chain comprises a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region.
  • the heavy chain constant region comprises three domains, CH1 , CH2 and CH3.
  • Each light chain comprises a light chain variable region (abbreviated herein as LCVR or V L ) and a light chain constant region.
  • the light chain constant region comprises one domain (C L 1).
  • the V H and V L regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR).
  • CDRs complementarity determining regions
  • Each V H and V L is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1 , CDR1 , FR2, CDR2, FR3, CDR3, FR4.
  • the FRs of the anti-AAV antibody or anti-cell surface molecule antibody may be identical to the human germline sequences or may be naturally or artificially modified.
  • An amino acid consensus sequence may be defined based on a side-by-side analysis of two or more CDRs.
  • antibody also includes antigen-binding fragments of full antibody molecules.
  • antigen-binding fragment of an antibody, “antigen-binding portion” of an antibody, and the like, as used herein, include any naturally occurring, enzymatically obtainable, synthetic, or genetically engineered polypeptide or glycoprotein that specifically binds to an antigen to form a complex.
  • Antigen-binding fragments of an antibody may be derived, e.g., from full antibody molecules using any suitable standard techniques such as proteolytic digestion or recombinant genetic engineering techniques involving the manipulation and expression of DNA encoding antibody variable and optionally constant domains.
  • DNA is known and/or is readily available from, e.g., commercial sources, DNA libraries (including, e.g., phage-antibody libraries), or can be synthesized.
  • the DNA may be sequenced and manipulated chemically or by using molecular biology techniques, for example, to arrange one or more variable and/or constant domains into a suitable configuration, or to introduce codons, create cysteine residues, modify, add or delete amino acids, etc.
  • Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; (vi) dAb fragments; and (vii) minimal recognition units consisting of the amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity determining region (CDR) such as a CDR3 peptide), or a constrained FR3- CDR3-FR4 peptide.
  • CDR complementarity determining region
  • engineered molecules such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g., monovalent nanobodies, bivalent nanobodies, etc.), small modular immunopharmaceuticals (SMIPs), and shark variable IgNAR domains, are also encompassed within the expression "antigenbinding fragment," as used herein.
  • SMIPs small modular immunopharmaceuticals
  • An antigen-binding fragment of an antibody will typically comprise at least one variable domain.
  • the variable domain may be of any size or amino acid composition and will generally comprise at least one CDR which is adjacent to or in frame with one or more framework sequences.
  • the V H and L domains may be situated relative to one another in any suitable arrangement.
  • the variable region may be dimeric and contain V H -V H , V H -V L or L-VL dimers.
  • the antigen-binding fragment of an antibody may contain a monomeric V H or V L domain.
  • an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain.
  • variable and constant domains that may be found within an antigen-binding fragment of an antibody of the present disclosure include: (i) VH-CH1 ; (ii) VH- C H 2; (iii) V H -C H 3; (iv) VH-C H 1-C H 2; (V) VH-C H 1 -CH2-C H 3; (vi) V H -C H 2-C H 3; (vii) V H -C L ; (viii) V L - C H 1 ; (ix) VL-C H 2; (X) V L -C H 3; (xi) VL-C H 1 -C H 2; (xii) VL-C H 1 -C H 2-CH3; (xiii) V L -C H 2-C H 3; and (xiv)
  • variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region.
  • a hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids which result in a flexible or semi-flexible linkage between adjacent variable and/or constant domains in a single polypeptide molecule.
  • an antigen-binding fragment of an antibody of the present disclosure may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non- covalent association with one another and/or with one or more monomeric VH or VL domain (e.g., by disulfide bond(s)).
  • antigen-binding fragments may be monospecific or multispecific (e.g., bispecific).
  • a bispecific antigen-binding fragment of an antibody will typically comprise at least two different variable domains, wherein each variable domain is capable of specifically binding to a separate antigen or to a different epitope on the same antigen.
  • Any multispecific antibody format including the non-limiting example formats disclosed herein, may be adapted for use in the context of an antigen-binding fragment of an antibody of the present disclosure using routine techniques available in the art.
  • CDR complementarity determining region
  • Exemplary conventions that can be used to identify the boundaries of CDRs include, e.g., the Kabat definition, the Chothia definition, the ABS definition and the IMGT definition. See, e.g., Kabat, 1991 , “Sequences of Proteins of Immunological Interest,” National Institutes of Health, Bethesda, Md. (Kabat numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol. 273:927-948 (Chothia numbering scheme); Martin et al., 1989, Proc. Natl. Acad. Sci. USA 86:9268-9272 (ABS numbering scheme); and Lefranc et ai, 2003, Dev. Comp. Immunol. 27:55-77 (IMGT numbering scheme). Public databases are also available for identifying CDR sequences within an antibody.
  • single chain Fv or “scFv” as used herein can refer to a polypeptide chain comprising the V H and V L domains of an antibody, where these domains are present in a single polypeptide chain.
  • Fab can refer to a pair of polypeptide chains, the first polypeptide chain comprising a variable heavy (VH) domain of an antibody N- terminal to a first constant domain (referred to herein as C1), and the second polypeptide chain comprising a variable light (VL) domain of an antibody N-terminal to a second constant domain (referred to herein as C2) capable of pairing with the first constant domain.
  • VH variable heavy
  • VL variable light domain of an antibody N-terminal to a second constant domain
  • the VH is N- terminal to the first constant domain (CH1) of the heavy chain
  • V L is N- terminal to the constant domain of the light chain (CL).
  • the Fabs of the disclosure can be arranged according to the native orientation or include domain substitutions or swaps on that facilitate correct VH and VL pairings, particularly where the antigen-binding molecules of the disclosure comprise non-identical Fabs.
  • correct chain pairing can be achieved by the use of universal light chains that can pair with both variable regions of a heterodimeric antigen-binding molecules of the disclosure.
  • universal light chain as used herein in the context of an antigen-binding molecule described herein can refer to a light chain polypeptide capable of pairing with the heavy chain region of a first Fab to form the first Fab and capable of pairing with the heavy chain region of a second Fab to form the second Fab. Universal light chains are also known as “common light chains.”
  • Fc domain can refer to a portion of the heavy chain that pairs with the corresponding portion of another heavy chain.
  • Fc region can refer to the region of antibody-based binding molecules formed by association of two heavy chain Fc domains. The two Fc domains within the Fc region may be the same or different from one another. In a native antibody the Fc domains are typically identical, but for the purpose of producing the antigen-binding molecules of the disclosure, one or both Fc domains might advantageously be modified to allow for heterodimerization.
  • the term “derived from” indicates a relationship between a first and a second molecule. It generally can refer to structural similarity between the first molecule and a second molecule and does not connote or include a process or source limitation on a first molecule that is derived from a second molecule.
  • the term “specifically binds” as used herein means that an antigen-binding molecule forms a complex with a target antigen that is relatively stable under physiologic
  • Specific binding can be characterized by a K D of about 5x10 -2 M or less (e.g., less than 5x10 -2 M, less than 10 -2 M, less than 5x10 2 M, less than 10 -3 M, less than 5x10 -4 M, less than 10 -4 M, less than 5x10 5 M, less than 10 5 M, less than 5x10 -6 M, less than 10 -6 M, less than 5x10 7 M, less than 10 7 M, less than 5x10 -8 M, less than 10 -8 M, less than 5x10 9 M, less than 10' 9 M, or less than 10 -1 ° M).
  • K D of about 5x10 -2 M or less (e.g., less than 5x10 -2 M, less than 10 -2 M, less than 5x10 2 M, less than 10 -3 M, less than 5x10 -4 M, less than 10 -4 M, less than 5x10 5 M, less than 10 5 M, less than 5x10 -6 M, less than 10 -6
  • an antigen-binding molecule or antigen-binding domain e.g., an antigen-binding molecule or antigen-binding domain
  • Methods for determining the binding affinity of an antibody or an antibody fragment, e.g., an antigen-binding molecule or antigen-binding domain, to a target antigen include, for example, equilibrium dialysis, surface plasmon resonance (e.g., Biacore assays), fluorescent-activated cell sorting (FACS) binding assays and the like.
  • An antigen-binding molecule that specifically binds to a target antigen from one species can, however, have cross-reactivity to the target antigen from one or more other species.
  • operably linked can refer to a functional relationship between two or more regions of a polypeptide chain in which the two or more regions are linked so as to produce a functional polypeptide.
  • nucleic acid or fragment thereof indicates that, when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 90%, and more preferably at least about 95%, 96%, 97%, 98% or 99% of the nucleotide bases, as measured by any well- known algorithm of sequence identity, such as FASTA, BLAST or Gap, as discussed below.
  • a nucleic acid molecule having substantial identity to a reference nucleic acid molecule may, in certain instances, encode a polypeptide having the same or substantially similar amino acid sequence as the polypeptide encoded by the reference nucleic acid molecule.
  • the term “substantial similarity” or “substantially similar” means that two peptide sequences, when optimally aligned, such as by the programs GAP or BESTFIT using default gap weights, share at least 95% sequence identity, even more preferably at least 98% or 99% sequence identity.
  • residue positions which are not identical differ by conservative amino acid substitutions.
  • a “conservative amino acid substitution” is one in which an amino acid residue is substituted by another amino acid residue having a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein.
  • the percent sequence identity or degree of similarity may be adjusted upwards to correct for the conservative nature of the substitution. Means for making this adjustment are well-known to those of skill in the art. See, e.g., Pearson (1994) Methods Mol. Biol. 24: 307-331 , herein incorporated by reference.
  • Examples of groups of amino acids that have side chains with similar chemical properties include (1) aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; (2) aliphatic-hydroxyl side chains: serine and threonine; (3) amide-containing side chains: asparagine and glutamine; (4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; (5) basic side chains: lysine, arginine, and histidine; (6) acidic side chains: aspartate and glutamate, and (7) sulfur-containing side chains are cysteine and methionine.
  • Preferred conservative amino acids substitution groups are: valine-leucine-isoleucine, phenylalaninetyrosine, lysine-arginine, alanine-valine, glutamate-aspartate, and asparagine-glutamine.
  • a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet et al. (1992) Science 256: 1443-1445, herein incorporated by reference.
  • a "moderately conservative" replacement is any change having a nonnegative value in the PAM250 log-likelihood matrix.
  • Sequence similarity for polypeptides is typically measured using sequence analysis software. Protein analysis software matches similar sequences using measures of similarity assigned to various substitutions, deletions and other modifications, including conservative amino acid substitutions.
  • GCG software contains programs such as Gap and Bestfit which can be used with default parameters to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a wild type protein and a mutein thereof. See, e.g., GCG Version 6.1 . Polypeptide sequences also can be compared using FASTA using default or recommended parameters, a program in GCG Version 6.1.
  • FASTA e.g., FASTA2 and FASTA3
  • FASTA2 and FASTA3 provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences (Pearson (2000) supra).
  • Another preferred algorithm when comparing a sequence of the disclosure to a database containing a large number of sequences from different organisms is the computer program BLAST, especially BLASTP or TBLASTN, using default parameters. See, e.g., Altschul et al. (1990) J. Mol. Biol. 215:403-410 and Altschul et al. (1997) Nucleic Acids Res. 25:3389-402, each herein incorporated by reference.
  • subject or "patient” as used herein includes all members of the animal kingdom including non-human primates and humans.
  • antibodies and antigen-binding fragments thereof that bind a capsid of an AAV particle also known as “anti-AAV antibodies” herein.
  • the capsid comprises any of various wild-type and/or non-wild-type AAV capsid protein(s) described herein.
  • the antibodies and/or antigenbinding fragments thereof bind an epitope on a capsid described herein.
  • the anti-AAV antibodies provided herein, or antigen-binding portions thereof may be included as part of a multispecific antigen-binding molecule, e.g., a multispecific antibody or multispecific antigenbinding fragment thereof, described herein.
  • AAV is an abbreviation for adeno-associated virus and may be used to refer to the virus itself or derivatives thereof.
  • AAVs are members of the Parvovirus family of small, nonenveloped, single-stranded DNA viruses.
  • ITR inverted terminal repeats
  • ORFs open reading frames
  • the wildtype rep reading frame encodes four proteins of molecular weight 78 kD (“Rep78”), 68 kD (“Rep68”), 52 kD (“Rep52”) and 40 kD (“Rep 40”).
  • Rep78 and Rep68 are transcribed from the p5 promoter, and Rep52 and Rep40 are transcribed from the p19 promoter. These proteins function mainly in regulating the transcription and replication of the AAV genome.
  • the wildtype cap reading frame encodes three structural (capsid) viral proteins (VPs) having molecular weights of 83-85 kD (VP1), 72-73 kD (VP2) and 61-62 kD (VP3). More than 80% of total proteins in an AAV virion (capsid) comprise VP3; in mature virions VP1 , VP2 and VP3 are found at relative abundance of approximately 1 :1 :10, although ratios of 1 :1 :8 have been reported. Padron et al. (2005) J. Virology 79:5047-58.
  • AAV encompasses all subtypes and both naturally occurring and modified forms (e.g., recombinant forms), except where stated otherwise.
  • AAV includes primate AAV (e.g., AAV type 1 (AAV1), primate AAV type 2 (AAV2), primate AAV type 3 (AAV3), primate AAV3B, primate AAV type 4 (AAV4), primate AAV type 5 (AAV5), primate AAV type 6 (AAV6), primate AAV6.2, primate AAV type 7 (AAV7), primate AAV type 8 (AAV8), primate AAV type 9 (AAV9), AAV10, AAV type hu11 (AAV hu11), AAV11, AAV12, AAV13, AAVDJ, Anc80L65, AAV2G9, AAVLK03, AAV type rh32.33 (AAVrh.32.33), AAV retro (AAV retro), AAV PHP.B, AAV PHP.eB
  • capsid protein includes a protein that is part of the capsid of the virus.
  • the capsid proteins are generally referred to as VP1 , VP2 and/or VP3, and may be encoded by the single cap gene.
  • the three AAV capsid proteins can be produced in nature an overlapping fashion from the cap ORF alternative translational start codon usage, although all three proteins use a common stop codon.
  • the ORF of a wildtype cap gene encodes from 5’ to 3’ three alternative start codons: ‘‘the VP1 start codon,” “the VP2 start codon,” and “the VP3 start codon”; and one “common stop codon”.
  • VP1 The largest viral protein, VP1 , is generally encoded from the VP1 start codon to the “common stop codon.”
  • VP2 is generally encoded from the VP2 start codon to the common stop codon.
  • VP3 is generally encoded from the VP3 start codon to the common stop codon.
  • VP1 comprises at its N-terminus sequence that it does not share with the VP2 or VP3, referred to as the VP1-unique region (VP1-u).
  • the VP1-u region is generally encoded by the sequence of a wildtype cap gene starting from the VP1 start codon to the “VP2 start codon.”
  • VP1-u comprises a phospholipase A2 domain (PLA2), which may be important for infection, as well as nuclear localization signals which may aid the virus in targeting to the nucleus for uncoating and genome release.
  • PHA2 phospholipase A2 domain
  • the VP1 , VP2, and VP3 capsid proteins share the same C-terminal sequence that makes up the entirety of VP3, which may also be referred to herein as the VP3 region.
  • the VP3 region is encoded from the VP3 start codon to the common stop codon.
  • VP2 has an additional ⁇ 60 amino acids that it shares with the VP1 .
  • an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described may bind to an epitope on the capsid.
  • the antibody may comprise any of the antibodies, e.g., multispecific antibodies, such as bispecific antibodies, which bind to the capsid of an AAV particle disclosed herein.
  • a multispecific antibody disclosed herein may comprise, for example, comprise a first binding domain that binds to a capsid of an AAV particle.
  • the first binding domain binds to an epitope on the capsid of the AAV particle.
  • the AAV particle capsid may comprise wild-type and/or non-wildtype AAV capsid proteins.
  • the epitope may comprise any of various serotypespecific or serotype-non-specific (i.e., “universal”) epitopes understood by one of ordinary skill in the art.
  • the epitope may comprise, e.g., any amino acid residues set forth in Tables 19-26, or variants of variants, derivatives or epitopes combinations thereof.
  • an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope on the capsid which is comprised of any amino acid residues of a capsid protein VP1 , VP2 or VP3, or a combination thereof.
  • the AAV particle can be derived from any AAV serotype described herein.
  • an antibody, or an antigen-binding fragment thereof can bind to any amino acid residue, or any combination thereof, of any variable region of a capsid, or any combination thereof, e.g., a variable region comprised of a capsid protein VP1 , VP2 or VP3, or a combination thereof (e.g., variable region I, II, III, IV, V, VI, VII, VIII, IX, or a combination thereof, as described in Emmanuel, et al., Journal of Virology, 2022, 96, 3).
  • an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV1 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof.
  • the antibody, or an antigen-binding fragment thereof may bind to AAV1 at any of residues 456-459, 492-499, 582, 583, 588- 591 , 593-595, 597, or any combination thereof, as described in Tseng, et al., Front Immunol. 2014, 5: 9.
  • an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV2 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof.
  • the antibody, or an antigen-binding fragment thereof may bind to AAV2 at any of residues 253, 254, 258, 261-264, 272-281, 369-378, 381 , 384, 385, 474-483, 492-502, 534, 548, 556, 560-573, 585-589, 601-610, 658-660, 708, 717, or any combination thereof, as described in Tseng, et al., Front Immunol. 2014, 5: 9.
  • an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV5 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof.
  • the antibody, or an antigen-binding fragment thereof may bind to AAV5 at any of residues 246, 254-261 , 374, 375, 483, 485- 492, 494, 496, 499-501 , 530, 532-538, 653, 654, 656, 657, 704-708, or any combination thereof as described in Tseng, et al., Front Immunol. 2014, 5: 9.
  • an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV8 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof.
  • the antibody, or an antigen-binding fragment thereof may bind to AAV8 at any of residues 586-591 or any combination thereof as described in Tseng, et al., Front Immunol. 2014, 5: 9.
  • an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV9 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof.
  • the antibody, or an antigen-binding fragment thereof may bind to AAV9 at any of residues 221 , 228, 246-248, 250-256, 258- 260, any of residues 262-273 of variable region I, any of residues 274, 275, 278, 291 , 293, 324, 325, any of residues 327-333 of variable region II, any of residues 334, 335, 338, 341 , 363-365, 369-373, 375, 376, any of residues 382-387, 389, 391 of variable region III, any of residues 438-441 , 443, any of residues 446, 448, 449, 451-460, 462, 464-473 of variable region IV, any of residues 488, 491-501 , 503-506, 510-515 of variable region V, any of residues 528-534, 545 of variable region VI, any of residues 547-560 of variable region VII, residue 572, any of residues 579, 584, 5
  • ITR inverted terminal repeat
  • the phrase “inverted terminal repeat” or “ITR” includes symmetrical nucleic acid sequences in the genome of adeno-associated viruses required for efficient replication. ITR sequences are located at each end of the AAV DNA genome. The ITRs serve as the origins of replication for viral DNA synthesis and are essential cis components for generating AAV particles, e.g., packaging into AAV particles.
  • AAV ITR comprise recognition sites for replication proteins Rep78 or Rep68.
  • a "D" region of the ITR comprises the DNA nick site where DNA replication initiates and provides directionality to the nucleic acid replication step.
  • An AAV replicating in a mammalian cell typically comprises two ITR sequences.
  • a single ITR may be engineered with Rep binding sites on both strands of the “A” regions and two symmetrical D regions on each side of the ITR palindrome.
  • Such an engineered construct on a double-stranded circular DNA template allows Rep78 or Rep68 initiated nucleic acid replication that proceeds in both directions.
  • a single ITR is sufficient for AAV replication of a circular particle.
  • the rep encoding sequence encodes a Rep protein or Rep protein equivalent that is capable of binding an ITR comprised on the transfer plasmid.
  • the Cap proteins of the disclosure when expressed with appropriate Rep proteins by a packaging cell, may encapsidate a transfer plasmid comprising a nucleotide of interest and an even number of two or more ITR sequences.
  • a transfer plasmid comprises one ITR sequence.
  • a transfer plasmid comprises two ITR sequences.
  • Rep proteins may be expressed from more than one ORF comprising nucleotide sequence encoding any combination of Rep78, Rep68, Rep 52 and/or Rep40 by use of separate nucleotide sequences operably linked to at least one expression control sequence for expression in a viral replication cell, each producing one or more of Rep78, Rep68, Rep 52 and/or Rep40 Rep proteins.
  • Rep proteins may be expressed individually from an ORF comprising a nucleotide sequence encoding any one of Rep78, Rep68, Rep 52, or Rep40 by use of separate nucleotide sequences operably linked to one expression control sequence for expression in a packaging cell, each producing only one Rep78, Rep68, Rep 52, or Rep40 Rep protein.
  • Rep proteins may be expressed from one ORF comprising nucleotide sequences encoding Rep78 and Rep52 Rep proteins operably linked to at least one expression control sequence for expression in a viral replication cell each producing Rep78 and Rep52 Rep protein.
  • a “chimeric AAV capsid protein” includes an AAV capsid protein that comprises amino acid sequences, e.g., portions, from two or more different AAV and that is capable of forming and/or forms an AAV viral capsid/viral particle.
  • a chimeric AAV capsid protein is encoded by a chimeric AAV capsid gene, e.g., a chimeric nucleotide comprising a plurality, e.g., at least two, nucleic acid sequences, each of which plurality is identical to a portion of a capsid gene encoding a capsid protein of distinct AAV, and which plurality together encodes a functional chimeric AAV capsid protein.
  • a chimeric capsid protein comprises one or more portions from a capsid protein of that AAV and one or more portions from a capsid protein of a different AAV.
  • a chimeric AAV2 capsid protein includes a capsid protein comprising one or more portions of a VP1 , VP2, and/or VP3 capsid protein of AAV2 and one or more portions of a VP1 , VP2, and/or VP3 capsid protein of a different AAV.
  • Table 1 sets forth the amino acid sequence identifiers of the heavy chain variable regions (HCVRs) and light chain variable regions (LCVRs), heavy chain complementarity determining regions (HCDR1 , HCDR2 and HCDR3), and light chain complementarity determining regions (LCDR1 , LCDR2 and LCDR3), as well as heavy chain (HC) and light chain (LC) of the exemplary anti-AAV antibodies and antigenbinding fragments.
  • HCVRs heavy chain variable regions
  • LCVRs light chain variable regions
  • HCDR1 , HCDR2 and HCDR3 heavy chain complementarity determining regions
  • LCDR1 , LCDR2 and LCDR3 light chain complementarity determining regions
  • Table 2 sets forth the sequence identifiers of the nucleic acid molecules encoding the HCVRs, LCVRs, HCDR1 , HCDR2, HCDR3, LCDR1 , LCDR2 LCDR3, HC and LC of the exemplary anti-AAV antibodies and antigen-binding fragments described herein.
  • Corresponding Fab and “standard mAb” i.e., mAb comprising a constant region derived from lgG4 subclass
  • Non-limiting examples of amino acid sequences and nucleotide sequences of the anti-AAV antibodies are also listed below.

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Abstract

L'invention concerne des anticorps anti-virus adéno-associés (AAV) et des fragments d'antigène de ceux-ci, ainsi que des anticorps multispécifiques (par exemple, des anticorps bispécifiques) qui se lient à la fois à une capside d'une particule d'AAV et à une molécule sur une surface cellulaire, des complexes moléculaires associés, des matrices d'affinité et des compositions pharmaceutiques, et leurs méthodes d'utilisation.
PCT/US2023/084372 2022-12-16 2023-12-15 Molécules de liaison à l'antigène qui se lient à des particules d'aav et utilisations WO2024130175A2 (fr)

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