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

Caroline Comte, Yann Tonin, Anne-Marie Heckel-Mager, Abdeldjalil Boucheham, Alexandre Smirnov, Karine Auré, Anne Lombès, Robert P Martin, Nina Entelis, Ivan Tarassov

Nucleic acids research 2013 Jan 07

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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 oligoribonucleotides complementary to mutant mtDNA region can specifically reduce the proportion of mtDNA bearing a large deletion associated with the Kearns Sayre Syndrome in cultured transmitochondrial cybrid cells. These findings may be relevant to developing of a new tool for therapy of mtDNA associated diseases.

Citation

Caroline Comte, Yann Tonin, Anne-Marie Heckel-Mager, Abdeldjalil Boucheham, Alexandre Smirnov, Karine Auré, Anne Lombès, Robert P Martin, Nina Entelis, Ivan Tarassov. Mitochondrial targeting of recombinant RNAs modulates the level of a heteroplasmic mutation in human mitochondrial DNA associated with Kearns Sayre Syndrome. Nucleic acids research. 2013 Jan 07;41(1):418-33