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Therapeutic genome editing: prospects and challenges

Nature Medicine volume 21, pages 121131 (2015) | Download Citation

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Abstract

Recent advances in the development of genome editing technologies based on programmable nucleases have substantially improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress toward developing programmable nuclease–based therapies as well as future prospects and challenges.

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Acknowledgements

The authors would like to thank J. Gootenberg, O. Abudayyeh, F. Ran and C. Men for critical reading of the manuscript, and all members of the Zhang lab for helpful discussions. D.B.T.C. is supported by award number T32GM007753 from the National Institute of General Medical Sciences. R.J.P. is supported by a National Science Foundation (NSF) Graduate Research Fellowship under grant number 1122374. F.Z. is supported by the National Institute of Mental Health through a US National Institutes of Health (NIH) Director's Pioneer Award (DP1-MH100706); the National Institute of Neurological Disorders and Stroke through an NIH Transformative R01 grant (R01-NS 07312401); an NSF Waterman Award; and the Keck, Damon Runyon, Searle Scholars, Klingenstein, Vallee, Merkin, and Simons Foundations. F.Z. is also supported by Bob Metcalfe. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the NIH.

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Affiliations

  1. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • David Benjamin Turitz Cox
    • , Randall Jeffrey Platt
    •  & Feng Zhang
  2. Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • David Benjamin Turitz Cox
  3. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • David Benjamin Turitz Cox
  4. McGovern Institute for Brain Research at MIT, Cambridge, Massachusetts, USA.

    • David Benjamin Turitz Cox
    • , Randall Jeffrey Platt
    •  & Feng Zhang
  5. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Randall Jeffrey Platt
    •  & Feng Zhang
  6. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Randall Jeffrey Platt
    •  & Feng Zhang

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Competing interests

F.Z. is a founder and scientific advisor of Editas Medicine and a scientific advisor of Horizon Discovery.

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Correspondence to Feng Zhang.

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https://doi.org/10.1038/nm.3793

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