Wang Mingyao, Fu Pengchong, Chen Ziheng, Wang Xiangnan, Ma Hanhui, Zhang Xuedi, Gao Guanjun
Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China.
Department of Cell Biology, School of Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu Province, 215123, China.
Genome Biol. 2025 Mar 11;26(1):53. doi: 10.1186/s13059-025-03523-8.
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.
染色体重排，如易位、缺失和倒位，是众多遗传疾病和癌症的基础，但对这些重排进行精确工程改造仍然具有挑战性。在此，我们提出了一种基于CRISPR的同源重组介导的重排（HRMR）策略，该策略利用同源供体模板来对齐和修复断裂的染色体末端。与非同源末端连接相比，HRMR的效率提高了约80倍，实现了超过95%的同源重组。在多个基因座和细胞系中得到验证，HRMR能够实现高效且准确的染色体重排。活细胞成像显示，同源供体介导染色体末端靠近，提高了重排效率。因此，HRMR为疾病建模、染色体生物学和治疗应用提供了一个强大的工具。
