Enhanced mitochondrial DNA editing in mice using nuclear-exported TALE-linked deaminases and nucleases
2022
Seonghyun Lee | Hyunji Lee | Gayoung Baek | Eunji Namgung | Joo Min Park | Sanghun Kim | Seongho Hong | Jin-Soo Kim
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.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by Directory of Open Access Journals