Aksoy, Y. A. et al. Commun. Biol. 2, 198 (2019)
CRISPR-Cas9 gene editing strategies rely on the activation of the DNA repair pathway after the generation of double strand breaks (DSBs). Non-homologous DNA end-joining (NHEJ) dominates the DNA repair pathway, which limits the efficiency of homology-directed repair (HDR), the alternative pathway allowing precise and high-fidelity gene targeting. In a new study, a team of investigators from Australia developed an in vivo visual reporter assay to quantify HDR-mediated events at single-cell resolution in zebrafish. They used this system to identify chemical compounds that shift the DNA repair equilibrium in favor of HDR, and showed that DNA-dependent protein kinase inhibitor NU7441, which blocks NHEJ, can increase precise CRISPR-mediated gene editing up to 13.4-fold.
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Le Bras, A. Enhancing gene editing in zebrafish. Lab Anim 48, 234 (2019). https://doi.org/10.1038/s41684-019-0359-x
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DOI: https://doi.org/10.1038/s41684-019-0359-x