College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Zhejiang University Cancer Center, Hangzhou 310058, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Aug 25;52(4):460-472. doi: 10.3724/zdxbyxb-2023-0129.
Mitochondrial DNA (mtDNA) mutations result in a variety of genetic diseases. As an emerging therapeutic method, mtDNA editing technology recognizes targets more based on the protein and less on the nucleic acid. Although the protein recognition type mtDNA editing technology represented by zinc finger nuclease technology, transcription activator like effector nuclease technology and base editing technology has made some progress, the disadvantages of complex recognition sequence design hinder further popularization. Gene editing based on nucleic acid recognition by the CRISPR system shows superiority due to the simple structure, easy design and modification. However, the lack of effective means to deliver nucleic acids into mitochondria limits application in the field of mtDNA editing. With the advances in the study of endogenous and exogenous import pathways and the deepening understanding of DNA repair mechanisms, growing evidence shows the feasibility of nucleic acid delivery and the broad application prospects of nucleic acid recognition type mtDNA editing technology. Based on the classification of recognition elements, this article summarizes the current principles and development of mitochondrial gene editing technology, and discusses its application prospects.
线粒体 DNA（mtDNA）突变导致多种遗传性疾病。作为一种新兴的治疗方法，mtDNA 编辑技术更多地基于蛋白质而非核酸来识别靶标。尽管以锌指核酸酶技术、转录激活因子样效应核酸酶技术和碱基编辑技术为代表的蛋白质识别型 mtDNA 编辑技术取得了一些进展，但复杂的识别序列设计的缺点阻碍了其进一步推广。基于 CRISPR 系统对核酸识别的基因编辑因其结构简单、设计和修饰方便而显示出优越性。然而，缺乏有效的方法将核酸递送到线粒体中限制了其在 mtDNA 编辑领域的应用。随着对内源和外源导入途径的研究进展以及对 DNA 修复机制的深入了解，越来越多的证据表明核酸递送的可行性和核酸识别型 mtDNA 编辑技术的广阔应用前景。本文基于识别元件的分类，总结了线粒体基因编辑技术的现状和发展，并讨论了其应用前景。
