Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.

ABSTRACT: CRISPR/Cas9-mediated gene editing has great potential utility for treating genetic diseases. However, its therapeutic applications are limited by unintended genomic alterations arising from DNA double-strand breaks and random integration of exogenous DNA. In this study, we propose NICER, a method for correcting heterozygous mutations that employs multiple nicks (MNs) induced by Cas9 nickase and a homologous chromosome as an endogenous repair template. Although a single nick near the mutation site rarely leads to successful gene correction, additional nicks on homologous chromosomes strongly enhance gene correction efficiency via interhomolog homologous recombination (IH-HR). This process partially depends on BRCA1 and BRCA2, suggesting the existence of several distinct pathways for MN-indu

SUBMITTER: Tomita A 

PROVIDER: S-EPMC10504326 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature