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Lookup NU author(s): Dr Jim StewartORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Research, 2018.
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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 transfer RNAAla levels, was restored by the treatment. These results showed that mitoTALENs, when expressed in affected tissues, could revert disease-related phenotypes in mice.
Author(s): Bacman SR, Kauppila JHK, Pereira CV, Nissanka N, Miranda M, Pinto M, Williams SL, Larsson NG, Stewart JB, Moraes CT
Publication type: Article
Publication status: Published
Journal: Nature Medicine
Print publication date: 01/11/2018
Online publication date: 24/09/2018
Acceptance date: 26/07/2018
Date deposited: 12/11/2020
ISSN (electronic): 1546-170X
Publisher: Nature Research
PubMed id: 30250143
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