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Programmable RNA-guided enzymes for next-generation genome editing

RNA-guided recombinase enzymes have been discovered that herald a new chapter for genome editing — enabling the insertion, inversion or deletion of long DNA sequences at user-specified genome positions.
  1. Connor J. Tou

    1. Connor J. Tou is at the Center for Genomic Medicine and in the Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA, and in the Biological Engineering Program, Massachusetts Institute of Technology, Cambridge, Massachusetts.

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  2. Benjamin P. Kleinstiver

    1. Benjamin P. Kleinstiver is at the Center for Genomic Medicine and in the Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA, and in the Department of Pathology, Harvard Medical School, Boston, Massachusetts.

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A long-standing aspiration for biologists has been to develop programmable methods to rearrange long DNA sequences in genomes. This capability would allow kilobase-scale DNA sequences to be inserted, inverted, deleted or moved to user-specified genome locations in cells in a single step. Recombinase and transposase enzymes that mediate genomic rearrangements of large sequences have therefore been studied intensively, but it has been challenging to reprogram these enzymes to precisely target user-specified genomic sites. Two papers in Nature1,2 now report the characterization of recombinases that are guided by a ‘bridge’ RNA molecule, and can thereby be reprogrammed to enable new genome-editing capabilities.

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Nature 630, 827-828 (2024)

doi: https://doi.org/10.1038/d41586-024-01461-2

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Competing Interests

C.J.T. and B.P.K. are inventors on patents or patent applications filed by Mass General Brigham (MGB) that describe genome engineering technologies. B.P.K. is a consultant for EcoR1 capital and Novartis Venture Fund, and is on the scientific advisory boards of Acrigen Biosciences, Life Edit Therapeutics and Prime Medicine. B.P.K. has a financial interest in Prime Medicine, a company developing therapeutic CRISPR–Cas technologies for gene editing. B.P.K.’s interests were reviewed and are managed by Massachusetts General Hospital and MGB in accordance with their conflict-of-interest policies.

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