ArticleNature communications2023
Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 16 citations in OpenAlex.
- Application of Gene Editing Technology in Poultry.Veterinary sciences · 2026Review
- Repair of replication-dependent double-strand breaks differs between the leading and lagging strands.Molecular cell · 2025Article
- Review
- CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy.Journal of translational medicine · 2024Review
- Review
- Homologous recombination contributes to the repair of acetaldehyde-induced DNA damage.Cell cycle (Georgetown, Tex.) · 2024Article
- Gene editing in small and large animals for translational medicine: a review.Animal reproduction · 2024Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
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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-induced IH-HR. According to a genomic analysis, NICER rarely induces unintended genomic alterations. Furthermore, NICER restores the expression of disease-causing genes in cells derived from genetic diseases with compound heterozygous mutations. Overall, NICER provides a precise strategy for gene correction.
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