Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33608520.
- Also identified by DOI 10.1038/s41467-021-21464-1 and PMC identifier 7895935.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddA<sub>tox</sub>, 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.
Medical subject headings
- DNA, Mitochondrial
- Gene Editing
- Genes, Mitochondrial