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

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Authors

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

Issue Date
2022-10-12
Citation
Genome Biology. 2022 Oct 12;23(1):211
Abstract
Abstract
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.
URI
https://doi.org/10.1186/s13059-022-02782-z

https://hdl.handle.net/10371/186387
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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