Abstract
AbstractThe efficiency of homology-directed repair (HDR) plays a crucial role in the development of animal models and gene therapy. We demonstrate that microhomology-mediated end-joining (MMEJ) constitutes a substantial proportion of DNA repair during CRISPR-mediated gene editing. Using CasRx to downregulate a key MMEJ factor, Polymerase Q (Polq), we improve the targeted integration efficiency of linearized DNA fragments and single-strand oligonucleotides (ssODN) in mouse embryos and offspring. CasRX-assisted targeted integration (CATI) also leads to substantial improvements in HDR efficiency during the CRISPR/Cas9 editing of monkey embryos. We present a promising tool for generating monkey models and developing gene therapies for clinical trials.
Funder
Shanghai Municipal Science and Technology Major Project
the Strategic Priority Research Program of the Chinese Academy of Sciences
the Basic Frontier Scientific Research Program of CAS
National Natural Science Foundation of China Grant
National Key Research and Development Program of China
China National Postdoctoral Program for Innovative Talents
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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