Jackson Christopher B, Turnbull Doug M, Minczuk Michal, Gammage Payam A
Stem Cells and Metabolism, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Trends Mol Med. 2020 Jul;26(7):698-709. doi: 10.1016/j.molmed.2020.02.006. Epub 2020 Mar 26.
Mutations of mitochondrial DNA (mtDNA) often underlie mitochondrial disease, one of the most common inherited metabolic disorders. Since the sequencing of the human mitochondrial genome and the discovery of pathogenic mutations in mtDNA more than 30 years ago, a movement towards generating methods for robust manipulation of mtDNA has ensued, although with relatively few advances and some controversy. While developments in the transformation of mammalian mtDNA have stood still for some time, recent demonstrations of programmable nuclease-based technology suggest that clinical manipulation of mtDNA heteroplasmy may be on the horizon for these largely untreatable disorders. Here we review historical and recent developments in mitochondrially targeted nuclease technology and the clinical outlook for treatment of hereditary mitochondrial disease.
线粒体DNA（mtDNA）突变往往是线粒体疾病的基础，线粒体疾病是最常见的遗传性代谢紊乱疾病之一。自30多年前人类线粒体基因组测序以及mtDNA致病突变被发现以来，人们一直在努力开发对mtDNA进行有效操作的方法，尽管进展相对较少且存在一些争议。虽然哺乳动物mtDNA转化技术的发展在一段时间内停滞不前，但最近基于可编程核酸酶技术的示范表明，对于这些基本上无法治疗的疾病，对mtDNA异质性进行临床操作可能即将实现。在此，我们回顾线粒体靶向核酸酶技术的历史和最新进展以及遗传性线粒体疾病的临床治疗前景。
