title: 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 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.
authors.affiliation: Department of Molecular and Cellular Genetics, UMR Génétique Moléculaire, Génomique, Microbiologie, CNRS, Université de Strasbourg, Strasbourg, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Comte
authors.forename: Yann
authors.initials: Y
authors.lastname: Tonin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Heckel-Mager
authors.forename: Abdeldjalil
authors.initials: A
authors.lastname: Boucheham
authors.forename: Alexandre
authors.initials: A
authors.lastname: Smirnov
authors.forename: Karine
authors.initials: K
authors.lastname: Auré
authors.forename: Anne
authors.initials: A
authors.lastname: Lombès
authors.forename: Robert P
authors.initials: RP
authors.lastname: Martin
authors.forename: Nina
authors.initials: N
authors.lastname: Entelis
authors.forename: Ivan
authors.initials: I
authors.lastname: Tarassov
mesh_terms: D000293:Adolescent; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis* / Q000737:chemistry; D005822:Genetic Vectors / Q000737:chemistry; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D009843:Oligoribonucleotides / Q000737:chemistry / Q000378:metabolism*; D034443:RNA Transport; D014162:Transfection
chemical_list: D004272:DNA, Mitochondrial; D009843:Oligoribonucleotides