Enhanced mitochondrial DNA editing in mice using nuclear-exported TALE-linked deaminases and nucleases

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Lee, Seonghyun; Lee, Hyunji; Baek, Gayoung; Namgung, Eunji; Park, Joo M.; Kim, Sanghun; Hong, Seongho; Kim, Jin-Soo

Issue Date
Genome Biology. 2022 Oct 12;23(1):211
We present two methods for enhancing the efficiency of mitochondrial DNA (mtDNA) editing in mice with DddA-derived cytosine base editors (DdCBEs). First, we fused DdCBEs to a nuclear export signal (DdCBE-NES) to avoid off-target C-to-T conversions in the nuclear genome and improve editing efficiency in mtDNA. Second, mtDNA-targeted TALENs (mitoTALENs) are co-injected into mouse embryos to cleave unedited mtDNA. We generated a mouse model with the m.G12918A mutation in the MT-ND5 gene, associated with mitochondrial genetic disorders in humans. The mutant mice show hunched appearances, damaged mitochondria in kidney and brown adipose tissues, and hippocampal atrophy, resulting in premature death.
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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