MitoTALEN reduces mutant mtDNA load and restores tRNA^Ala levels in a mouse model of heteroplasmic mtDNA mutation.

ABSTRACT: Mutations in the mitochondrial DNA (mtDNA) are responsible for several metabolic disorders, commonly involving muscle and the central nervous system¹. Because of the critical role of mtDNA in oxidative phosphorylation, the majority of pathogenic mtDNA mutations are heteroplasmic, co-existing with wild-type molecules¹. Using a mouse model with a heteroplasmic mtDNA mutation², we tested whether mitochondrial-targeted TALENs (mitoTALENs)^3,4 could reduce the mutant mtDNA load in muscle and heart. AAV9-mitoTALEN was administered via intramuscular, intravenous, and intraperitoneal injections. Muscle and heart were efficiently transduced and showed a robust reduction in mutant mtDNA, which was stable over time. The molecular defect, namely a decrease in

SUBMITTER: Bacman SR 

PROVIDER: S-EPMC6942693 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature