Résumé :
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Duchenne and Becker muscular dystrophy (DMD, BMD) are caused by mutations in the dystrophin gene. In general, DMD mutations disrupt the reading frame and leadto prematurely aborted dystrophin synthesis; conversely, mutations that leave the reading frame intact lead to the production of low levels of internally truncated protein,which are sufficient to generate the milder BMD phenotype. This observation suggested that a therapeutic approach for DMD could be based on active intervention onprimary RNA processing ("exon-skipping"), aimed at restoring a viable reading frame.The most commonly used exon-skipping approach relies on the use of sequencespecificantisense oligonucleotides (AO), which binds to intron-exon boundaries and/or to splice enhancer elements.So far, virtually all AO designing procedures havebeen tested on intact dystrophin genes. However, there are clear indications that the genomic re-arrangements (deletion, duplications, point mutations, etc.) presentin patients can affect the efficiency of the desired skipping processes. In this work we hence decided to compare the efficiency of a set of AO in control and in DMDmyoblasts, obtained from patients carrying different types of mutations. Our data indicated that not only AO skipping efficiency varied greatly between intact and mutatedDMD genes, but also that at times patients' mRNA exhibited splicing patterns that could not be directly correlated to their specific genomic mutation.
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