O.6 Antisense approach for myotonic dystrophy

Abstract

Myotonic dystrophy type 1 (DM1) is caused by a dominant-negative pathogenic effects of RNA containing CUG expansions cause DM1. The knockdown of the CUG repeat RNA could be a major approach for the development of a gene therapy for DM1. The proof of principle regarding this approach was originally demonstrated in hDM1 myoblasts. We have shown that antisense RNAs are more efficient than shRNAs to target mutant DMPK RNAs and to restore a normal behavior to hDM1 myoblasts. In a DM1 mouse model, we showed that antisense RNAs can decreased up to 55% the levels of mutant transcripts, one month following a single i.m.