Tang Jinling, Du Kunzhao
Clinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
Jinshan Hospital Center for Neurosurgery, Jinshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 201508, China.
Cell Biosci. 2025 Jan 24;15(1):9. doi: 10.1186/s13578-025-01351-8.
In recent years, mitochondrial DNA (mtDNA) base editing systems have emerged as bioengineering tools. DddA-derived cytosine base editors (DdCBEs) have been developed to specifically induce C-to-T conversion in mtDNA by the fusion of sequence-programmable transcription activator-like effector nucleases (TALENs) or zinc-finger nucleases (ZFNs), and split deaminase derived from interbacterial toxins. Similar to DdCBEs, mtDNA adenine base editors have been developed with the ability to introduce targeted A-to-G conversions into human mtDNA. In this review, we summarize the principles of mtDNA base-editing systems and elaborate on the evolution of different platforms of mtDNA base editors, including their deaminase replacement, engineering of DddA variants, structure optimization and editing outcomes. Finally, we highlight their applications in animal models and human embroys and discuss the future developmental direction and challenges of mtDNA base editors.
近年来，线粒体DNA（mtDNA）碱基编辑系统已成为生物工程工具。通过融合序列可编程的转录激活因子样效应核酸酶（TALENs）或锌指核酸酶（ZFNs）以及源自细菌间毒素的分裂脱氨酶，已开发出DddA衍生的胞嘧啶碱基编辑器（DdCBEs），以特异性诱导mtDNA中的C到T转换。与DdCBEs类似，mtDNA腺嘌呤碱基编辑器也已开发出来，能够将靶向的A到G转换引入人类mtDNA。在这篇综述中，我们总结了mtDNA碱基编辑系统的原理，并详细阐述了mtDNA碱基编辑器不同平台的发展，包括它们的脱氨酶替换、DddA变体的工程改造、结构优化和编辑结果。最后，我们重点介绍了它们在动物模型和人类胚胎中的应用，并讨论了mtDNA碱基编辑器未来的发展方向和挑战。
