Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases.
Hyunji LeeSeonghyun LeeGayoung BaekAnnie KimBeum-Chang KangHuiyun SeoJin-Soo KimPublished in: Nature communications (2021)
DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddAtox, 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.
Keyphrases
- mitochondrial dna
- copy number
- oxidative stress
- highly efficient
- crispr cas
- genome wide
- electron transfer
- high fat diet induced
- escherichia coli
- dna methylation
- endothelial cells
- transcription factor
- dendritic cells
- regulatory t cells
- insulin resistance
- dna damage
- type diabetes
- skeletal muscle
- immune response
- dna repair
- climate change
- drug delivery
- human health
- toll like receptor
- type iii