Dystrophin rescue by trans-splicing: a strategy for DMD genotypes not eligible for exon skipping approaches.

ABSTRACT: RNA-based therapeutic approaches using splice-switching oligonucleotides have been successfully applied to rescue dystrophin in Duchenne muscular dystrophy (DMD) preclinical models and are currently being evaluated in DMD patients. Although the modular structure of dystrophin protein tolerates internal deletions, many mutations that affect nondispensable domains of the protein require further strategies. Among these, trans-splicing technology is particularly attractive, as it allows the replacement of any mutated exon by its normal version as well as introducing missing exons or correcting duplication mutations. We have applied such a strategy in vitro by using cotransfection of pre-trans-splicing molecule (PTM) constructs along with a reporter minigene containing part of the dystrophin ge

SUBMITTER: Lorain S 

PROVIDER: S-EPMC3783188 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature