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The promise and challenge of therapeutic genome editing

Abstract

Genome editing, which involves the precise manipulation of cellular DNA sequences to alter cell fates and organism traits, has the potential to both improve our understanding of human genetics and cure genetic disease. Here I discuss the scientific, technical and ethical aspects of using CRISPR (clustered regularly interspaced short palindromic repeats) technology for therapeutic applications in humans, focusing on specific examples that highlight both opportunities and challenges. Genome editing is—or will soon be—in the clinic for several diseases, with more applications under development. The rapid pace of the field demands active efforts to ensure that this breakthrough technology is used responsibly to treat, cure and prevent genetic disease.

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Fig. 1: Ex vivo and in vivo genome editing to treat human disease.
Fig. 2: The genome editing toolbox.
Fig. 3: Emerging tools.
Fig. 4: Editing the human germline.

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Acknowledgements

J.A.D. thanks M. Hochstrasser and M. Triplet for extensive expert assistance with manuscript editing, formatting, referencing and illustrations. D. Carroll, F. Urnov and R. Wilson provided comments on the manuscript. T. Tolpa created the artwork with input from M. Hochstrasser and E. Stahl, and with support from the Innovative Genomics Institute. J.A.D. is an investigator of the Howard Hughes Medical Institute (HHMI) and a Paul Allen Distinguished Investigator. In addition to funding from HHMI and the Paul Allen Frontiers Group, research in the Doudna laboratory is supported by the Defense Advanced Research Projects Agency (DARPA) (award HR0011-17-2-0043), the William M. Keck Foundation, a Collaborative MS Research Center Award from the National Multiple Sclerosis Society, the Centers for Excellence in Genomic Science of the National Institutes of Health under award number RM1HG009490, the Somatic Cell Genome Editing Program of the Common Fund of the National Institutes of Health under award number U01AI142817-02 and the National Science Foundation under award number 1817593.

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Correspondence to Jennifer A. Doudna.

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J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Intellia Therapeutics, Scribe Therapeutics and Mammoth Biosciences; a scientific adviser to Caribou Biosciences, Intellia Therapeutics, Scribe Therapeutics, Synthego, Inari and eFFECTOR Therapeutics; and a director of Johnson & Johnson. The Regents of the University of California have patents issued and pending for CRISPR-related technologies on which J.A.D. is an inventor.

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Peer review information Nature thanks R. Alta Charo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Doudna, J.A. The promise and challenge of therapeutic genome editing. Nature 578, 229–236 (2020). https://doi.org/10.1038/s41586-020-1978-5

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