Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing

doi:10.1186/s13059-025-03523-8

	Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing
	Wang, Mingyao1 ; Fu, Pengchong1 ; Chen, Ziheng1 ; Wang, Xiangnan1 ; Ma, Hanhui1 ; Zhang, Xuedi1,2 ; Gao, Guanjun1
	2025-03-11
发表期刊	GENOME BIOLOGY (IF:10.1[JCR-2023],16.5[5-Year])
ISSN	1474-760X
卷号	26 期号:1
发表状态	已发表
DOI	10.1186/s13059-025-03523-8
摘要	Chromosomal rearrangements, such as translocations, deletions, and inversions, underlie numerous genetic diseases and cancers, yet precise engineering of these rearrangements remains challenging. Here, we present a CRISPR-based homologous recombination-mediated rearrangement (HRMR) strategy that leverages homologous donor templates to align and repair broken chromosome ends. HRMR improves efficiency by approximately 80-fold compared to non-homologous end joining, achieving over 95% homologous recombination. Validated across multiple loci and cell lines, HRMR enables efficient and accurate chromosomal rearrangements. Live-cell imaging reveals that homologous donors mediate chromosome end proximity, enhancing rearrangement efficiency. Thus, HRMR provides a powerful tool for disease modeling, chromosomal biology, and therapeutic applications.
关键词	CRISPR-Cas9 Chromosome rearrangement Homologous recombination Double-strand DNA break repair
URL	查看原文
收录类别	SCI
语种	英语
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS记录号	WOS:001441786200001
出版者	BMC
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/503579
专题	生命科学与技术学院生命科学与技术学院_PI研究组_高冠军组生命科学与技术学院_硕士生生命科学与技术学院_博士生生命科学与技术学院_PI研究组_马涵慧组
通讯作者	Zhang, Xuedi; Gao, Guanjun
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Gene Editing Ctr, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 2.Soochow Univ, Suzhou Med Coll, Sch Basic Med Sci, Dept Cell Biol, Suzhou 215123, Jiangsu, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Wang, Mingyao,Fu, Pengchong,Chen, Ziheng,et al. Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing[J]. GENOME BIOLOGY,2025,26(1).
APA	Wang, Mingyao.,Fu, Pengchong.,Chen, Ziheng.,Wang, Xiangnan.,Ma, Hanhui.,...&Gao, Guanjun.(2025).Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing.GENOME BIOLOGY,26(1).
MLA	Wang, Mingyao,et al."Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing".GENOME BIOLOGY 26.1(2025).