In recent years mitochondrial DNA (mtDNA) has transitioned to greater prominence across diverse areas of biology and medicine. The recognition of mitochondria as a major biochemical hub, contributions of mitochondrial dysfunction to various diseases, and several high-profile attempts to prevent hereditary mtDNA disease through mitochondrial replacement therapy have roused interest in the organellar genome. Subsequently, attempts to manipulate mtDNA have been galvanized, although with few robust advances and much controversy. Re-engineered protein-only nucleases such as mtZFN and mitoTALEN function effectively in mammalian mitochondria, although efficient delivery of nucleic acids into the organelle remains elusive. Such an achievement, in concert with a mitochondria-adapted CRISPR/Cas9 platform, could prompt a revolution in mitochondrial genome engineering and biological understanding. However, the existence of an endogenous mechanism for nucleic acid import into mammalian mitochondria, a prerequisite for mitochondrial CRISPR/Cas9 gene editing, remains controversial.

近年来，线粒体 DNA (mtDNA) 在生物学和医学的各个领域变得越来越重要。线粒体作为主要生化中心的认识、线粒体功能障碍对各种疾病的影响，以及通过线粒体替代疗法预防遗传性线粒体 DNA 疾病的一些引人注目的尝试，引起了人们对细胞器基因组的兴趣。随后，操纵线粒体DNA的尝试不断涌现，尽管取得的进展很少，而且争议很大。重新设计的纯蛋白质核酸酶，如 mtZFN 和 mitoTALEN 在哺乳动物线粒体中有效发挥作用，尽管将核酸有效递送到细胞器中仍然难以捉摸。这一成就与线粒体适应的 CRISPR/Cas9 平台相结合，可能会引发线粒体基因组工程和生物学理解的一场革命。然而，核酸导入哺乳动物线粒体的内源机制（线粒体 CRISPR/Cas9 基因编辑的先决条件）是否存在仍然存在争议。