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Review
. 2023 Aug 9;11(3):101057.
doi: 10.1016/j.gendis.2023.06.026. eCollection 2024 May.

Mitochondrial diseases and mtDNA editing

Min Song  1 , Lingqun Ye  1 , Yongjin Yan  2 , Xuechun Li  1 , Xinglong Han  1 , Shijun Hu  1 , Miao Yu  1
Affiliations
Review

Mitochondrial diseases and mtDNA editing

Min Song et al. Genes Dis. .

Abstract

Mitochondrial diseases are a heterogeneous group of inherited disorders characterized by mitochondrial dysfunction, and these diseases are often severe or even fatal. Mitochondrial diseases are often caused by mitochondrial DNA mutations. Currently, there is no curative treatment for patients with pathogenic mitochondrial DNA mutations. With the rapid development of traditional gene editing technologies, such as zinc finger nucleases and transcription activator-like effector nucleases methods, there has been a search for a mitochondrial gene editing technology that can edit mutated mitochondrial DNA; however, there are still some problems hindering the application of these methods. The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing. In this paper, we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.

Keywords: Gene editing; Mitochondrial DNA mutation; Mitochondrialdisease; Transcription activator-like effector nucleases; Zinc finger nucleases.

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Figures

Fig. 1
Figure 1
Mitochondria are heterogeneous, and germ cells carrying mutant mitochondria are inherited in such a way that the number of mutant mitochondria acquired by each oocyte is different; only when the number of mutant mitochondria reaches a certain threshold the mutation leads to mitochondrial disease.
Fig. 2
Figure 2
Several mitochondrial editing tools. By fusing with mitochondria targeting sequence (MTS), mitochondria editing machinery can enter the mitochondria. In the mitochondria, ZFNs and TALENs bind to specific mtDNA sites according to their DNA binding sequences and exert nucleic acid endonuclease activity to break the mutated double-stranded mtDNA, thus allowing the mutated mtDNA to be cleaved. Cytosine base editing DdCBE is capable of single base editing of mitochondrial genes, converting C-G base pairs to T-A base pairs and correcting mutated mtDNA.
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