Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases.

ABSTRACT: DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddA_tox, transcription activator-like effector (TALE), and uracil glycosylase inhibitor (UGI), enable targeted C-to-T base conversions in mitochondrial DNA (mtDNA). Here, we demonstrate highly efficient mtDNA editing in mouse embryos using custom-designed DdCBEs. We target the mitochondrial gene, MT-ND5 (ND5), which encodes a subunit of NADH dehydrogenase that catalyzes NADH dehydration and electron transfer to ubiquinone, to obtain several mtDNA mutations, including m.G12918A associated with human mitochondrial diseases and m.C12336T that incorporates a premature stop codon, creating mitochondrial disease models in mice and demonstrating a potential for the treatment of mitochondrial disorders.

SUBMITTER: Lee H 

PROVIDER: S-EPMC7895935 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature