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Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson’s Disease, Glioma, and Schwannoma

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Abstract

Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson’s disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood–brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases.

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Acknowledgments

We thank Suzanne McDavitt for skilled editorial assistance and Dr. Bence György for insights into packaging of different length mRNAs into EVs. This work was supported by the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director, NCI U19 CA179563 (XOB) and Voices Against Brain Cancer (XOB & CPL).

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Authors and Affiliations

  1. Departments of Chemistry and Chemical Biology and Molecular Medicine, Cornell University, Ithaca, NY, 14853, USA

    Justin Hall & Richard A. Cerione

  2. Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA

    Justin Hall, Shilpa Prabhakar, Leonora Balaj, Charles P. Lai & Xandra O. Breakefield

  3. Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan

    Charles P. Lai

  4. Molecular Neurogenetics Unit, Massachusetts General Hospital-East, 13th Street, Building 149, Charlestown, MA, 02129, USA

    Xandra O. Breakefield

Authors
  1. Justin Hall
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  2. Shilpa Prabhakar
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  3. Leonora Balaj
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  4. Charles P. Lai
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  5. Richard A. Cerione
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  6. Xandra O. Breakefield
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Corresponding author

Correspondence to Xandra O. Breakefield.

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Hall, J., Prabhakar, S., Balaj, L. et al. Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson’s Disease, Glioma, and Schwannoma. Cell Mol Neurobiol 36, 417–427 (2016). https://doi.org/10.1007/s10571-015-0309-0

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  • DOI: https://doi.org/10.1007/s10571-015-0309-0

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