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Advances in genome editing through control of DNA repair pathways

Abstract

Eukaryotic cells deploy overlapping repair pathways to resolve DNA damage. Advancements in genome editing take advantage of these pathways to produce permanent genetic changes. Despite recent improvements, genome editing can produce diverse outcomes that can introduce risks in clinical applications. Although homology-directed repair is attractive for its ability to encode precise edits, it is particularly difficult in human cells. Here we discuss the DNA repair pathways that underlie genome editing and strategies to favour various outcomes.

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Fig. 1: Pathways of canonical double-stranded break repair (DSBR) and selected interventions to manipulate editing outcomes.
Fig. 2: Methods of enhancing precision DSBR.

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Acknowledgements

This work was supported by the Li Ka Shing Foundation (J.E.C., C.D.R. and C.D.Y.), the NIH New Innovator Program (DP2 HL141006, J.E.C.), the Heritage Medical Research Institute (C.D.R. and C.D.Y.), and the Fanconi Anemia Research Foundation (C.D.R. and C.D.Y.).

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Yeh, C.D., Richardson, C.D. & Corn, J.E. Advances in genome editing through control of DNA repair pathways. Nat Cell Biol 21, 1468–1478 (2019). https://doi.org/10.1038/s41556-019-0425-z

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