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論文
- タイトル
- タイトル（英）
- Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.
- 参照URL
- https://researchmap.jp/7000009079/published_papers/43518371
- 著者
- 著者（英）
- Akiko Tomita,Hiroyuki Sasanuma,Tomoo Owa,Yuka Nakazawa,Mayuko Shimada,Takahiro Fukuoka,Tomoo Ogi,Shinichiro Nakada
- 担当区分
- 概要
- 概要（英）
- 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.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Nature communications
- 巻
- 14
- 号
- 1
- 開始ページ
- 5607
- 終了ページ
- 5607
- 出版年月
- 2023年9月15日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1038/s41467-023-41048-5
- 共同研究・競争的資金等の研究課題
研究者
笹沼 博之
( )