Alterations in mitochondrial base editors enhance targeted editing efficiency for mouse model generation.

ABSTRACT: Mitochondrial DNA (mtDNA) base editors are powerful tools for investigating mitochondrial diseases. However, their editing efficiency can vary significantly depending on the target site within the mtDNA. In this study, we developed two improved versions of the mitochondrial adenine base editor (Hifi-sTALED and αnHifi-sTALED) by modifying components other than the TadA8e-V28R deaminase variant. These enhancements significantly increased editing efficiency while preserving minimal off-target effects across the transcriptome. Using these optimized editors, we achieved improved mtDNA editing in mouse embryos and successfully generated mt-Rnr1 mutant mice with high heteroplasmic loads. Functional analyses revealed that the mt-Rnr1 mutation impaired mitochondrial function, as indic

SUBMITTER: Hong S 

PROVIDER: S-EPMC12398210 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature