Mitochondrial targeting of recombinant RNAs modulates the level of a heteroplasmic mutation in human mitochondrial DNA associated with Kearns Sayre Syndrome

Abstract : Mitochondrial mutations, an important cause of incurable human neuromuscular diseases, are mostly heteroplasmic: mutated mitochondrial DNA is present in cells simultaneously with wild-type genomes, the pathogenic threshold being generally >70% of mutant mtDNA. We studied whether heteroplasmy level could be decreased by specifically designed oligoribonucleotides, targeted into mitochondria by the pathway delivering RNA molecules in vivo. Using mitochondrially imported RNAs as vectors, we demonstrated that oligoribo-nucleotides complementary to mutant mtDNA region can specifically reduce the proportion of mtDNA bearing a large deletion associated with the Kearns Sayre Syndrome in cultured transmito-chondrial cybrid cells. These findings may be relevant to developing of a new tool for therapy of mtDNA associated diseases.
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Nucleic Acids Research, Oxford University Press, 2013, 41 (1), pp.418-433. 〈10.1093/nar/gks965〉
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Caroline Comte, Yann Tonin, Anne-Marie Heckel-Mager, Abdeldjalil Boucheham, Alexandre Smirnov, et al.. Mitochondrial targeting of recombinant RNAs modulates the level of a heteroplasmic mutation in human mitochondrial DNA associated with Kearns Sayre Syndrome. Nucleic Acids Research, Oxford University Press, 2013, 41 (1), pp.418-433. 〈10.1093/nar/gks965〉. 〈hal-01587401〉

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