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Refining strategies to translate genome editing to the clinic

Abstract

Recent progress in developing programmable nucleases, such as zinc-finger nucleases, transcription activator–like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)–Cas nucleases, have paved the way for gene editing to enter clinical practice. This translation is a result of combining high nuclease activity with high specificity and successfully applying this technology in various preclinical disease models, including infectious disease, primary immunodeficiencies, hemoglobinopathies, hemophilia and muscular dystrophy. Several clinical gene-editing trials, both ex vivo and in vivo, have been initiated in the past 2 years, including studies that aim to knockout genes as well as to add therapeutic transgenes. Here we discuss the advances made in the gene-editing field in recent years, and specify priorities that need to be addressed to expand therapeutic genome editing to further disease entities.

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Figure 1: Designer-nuclease-induced genome editing.
Figure 2: Improving the specificity of engineered nucleases.
Figure 3: Production of an off-the-shelf CAR T cell product.
Figure 4: Roadmap: translating targeted genome editing into the clinic.

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Acknowledgements

We thank all members of the laboratories for helpful discussion. Current research in our labs is funded by the Federal Ministry of Education and Research (IFB—01EO0803; iMACnet—01EK1602B; HBV-TALE—01DG15005), the German Research Foundation (SFB1160—TP17), the European Commission's Horizon 2020 Program (SCIDNET—666908; CARAT—667980), Casebia Therapeutics (CAU-950-20140702) and the German Academic Exchange Service.

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Correspondence to Toni Cathomen.

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T.C. is a consultant for TRACR Hematology.

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Cornu, T., Mussolino, C. & Cathomen, T. Refining strategies to translate genome editing to the clinic. Nat Med 23, 415–423 (2017). https://doi.org/10.1038/nm.4313

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