Department of Physiology, Korea University College of Medicine, Seoul, 02841, Republic of Korea.
Laboratory Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, 28116, Cheongju, Republic of Korea.
Exp Mol Med. 2023 May;55(5):871-878. doi: 10.1038/s12276-023-00973-7. Epub 2023 May 1.
Mitochondria are of fundamental importance in programmed cell death, cellular metabolism, and intracellular calcium concentration modulation, and inheritable mitochondrial disorders via mitochondrial DNA (mtDNA) mutation cause several diseases in various organs and systems. Nevertheless, mtDNA editing, which plays an essential role in the treatment of mitochondrial disorders, still faces several challenges. Recently, programmable editing tools for mtDNA base editing, such as cytosine base editors derived from DddA (DdCBEs), transcription activator-like effector (TALE)-linked deaminase (TALED), and zinc finger deaminase (ZFD), have emerged with considerable potential for correcting pathogenic mtDNA variants. In this review, we depict recent advances in the field, including structural biology and repair mechanisms, and discuss the prospects of using base editing tools on mtDNA to broaden insight into their medical applicability for treating mitochondrial diseases.
线粒体在细胞程序性死亡、细胞代谢和细胞内钙离子浓度调节中具有重要意义，通过线粒体 DNA（mtDNA）突变导致的遗传性线粒体疾病会引起多种器官和系统的疾病。然而，在线粒体疾病治疗中发挥重要作用的 mtDNA 编辑仍然面临着许多挑战。最近，针对 mtDNA 碱基编辑的可编程编辑工具如来源于 DddA 的胞嘧啶碱基编辑器（DdCBEs）、转录激活因子样效应物（TALE）连接的脱氨酶（TALED）和锌指脱氨酶（ZFD）已经出现，它们具有纠正致病性 mtDNA 变异的巨大潜力。在这篇综述中，我们描述了该领域的最新进展，包括结构生物学和修复机制，并讨论了使用 mtDNA 碱基编辑工具的前景，以加深对其治疗线粒体疾病的医学应用的理解。
