The inability to precisely manipulate mammalian mitochondrial DNA has stalled our understanding of mitochondrial biology and the generation of cellular and animal models in which to study it. DNA base editing technologies have enabled the generation of a library of mitochondrial base editors that precisely ablate every protein-coding gene in the mouse mitochondrial genome.
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References
Gorman, G. S. et al. Mitochondrial diseases. Nat. Rev. Dis. Primers 2, 16080 (2016). A review article presenting an overview of mitochondrial diseases.
Silva-Pinheiro, P. & Minczuk, M. The potential of mitochondrial genome engineering. Nat. Rev. Genet. 23, 199–214 (2022). A review article that presents the advances of mitochondrial DNA engineering.
Mok, B. Y. et al. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature 583, 631–637 (2020). This paper reports the development of the mitochondrial DNA base editor, DdCBE.
Lei, Z. et al. Mitochondrial base editor induces substantial nuclear off-target mutations. Nature 606, 804–811 (2022). This paper reports the identification of nuclear off-target effects when using DdCBEs.
Silva-Pinheiro, P. et al. In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue. Nat. Commun. 13, 750 (2022). This paper reports the application of DdCBEs in vivo using viral delivery.
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This is a summary of: Silva-Pinheiro, P. et al. A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-022-00968-1 (2022).
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Base editing ablates all protein-coding genes of the mitochondrial genome in mouse cells. Nat. Biomed. Eng 7, 614–615 (2023). https://doi.org/10.1038/s41551-022-00986-z
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DOI: https://doi.org/10.1038/s41551-022-00986-z
