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

Autor: Seonghyun Lee, Hyunji Lee, Gayoung Baek, Eunji Namgung, Joo Min Park, Sanghun Kim, Seongho Hong, Jin-Soo Kim
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Genome Biology, Vol 23, Iss 1, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 1474-760X
DOI: 10.1186/s13059-022-02782-z
Popis: 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.
Databáze: Directory of Open Access Journals