不依赖DNA双链断裂的CRISPR技术研究进展

doi:10.3870/j.issn.1672-8009.2026.05.015

摘要/Abstract

摘要： 基因编辑技术能够精确修饰生物体基因组中的特定DNA片段,为疾病治疗、基因功能研究、基因检测和药物开发等开辟了新途径。传统CRISPR-Cas9基因编辑技术依赖DNA双链断裂（double-strand break,DSB）,其在修复过程中易诱发indel突变、具有细胞毒性且同源定向修复（homology-directed repair, HDR）效率低下,严重限制了其在精准医学中的应用。为解决以上问题,一系列不依赖DSB的新型CRISPR衍生技术应运而生。文章系统综述了碱基编辑器、引导编辑器及转座子类编辑器这三个代表性技术的原理、发展与应用,分析了它们如何利用机制创新来规避DSB,同时深入探讨了其在编辑效率、精度、适用范围与递送难度等方面的优势与局限,展望了编辑器的未来发展方向,指出小型化、效率提升与递送工具创新是推动该技术实现向临床转换的关键。

关键词: CRISPR-Cas9, 碱基编辑器, 引导编辑器, 转座子类编辑器

Abstract: Gene editing technology can precisely modify specific DNA segments in the genome of an organism, opening up new ways for disease treatment, gene function research, gene testing and drug development. Conventional CRISPR-Cas9 gene editing relies on DNA double-strand break（DSB）, whose repair processes are prone to inducing indel mutations, exhibit cytotoxicity, and demonstrate low efficiency in homology-directed repair, significantly limiting its applications in precision medicine. To overcome this limitation, a series of novel CRISPR-derived technologies independent of DSB have emerged. This review systematically summarizes the principles, development, and applications of three representative technologies： base editors, prime editors, and transposon-based editors, with a focus on analyzing how their mechanistic innovations circumvent DSB. It further explores their respective advantages and inherent limitations in terms of editing efficiency, precision, target scope, and delivery challenges. Finally, the review offers perspectives on future technological directions, highlighting that editor miniaturization, efficiency enhancement, and delivery tool innovation are key to advancing clinical translation in this field.

Key words: CRISPR-Cas9, base editors, prime editors, transposon-associated editors

中图分类号:

王瑞晗, 隋鲜鲜, 严钰锋. 不依赖DNA双链断裂的CRISPR技术研究进展[J]. 医学分子生物学杂志, 2026, 23(5): 592-599.

WANG Ruihan, SUI Xianxian, YAN Yufeng. Research Advances in CRISPR Technologies Independent of DNA Double-Strand Breaks[J]. Journal of Medical Molecular Biology, 2026, 23(5): 592-599.

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