Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs.

ABSTRACT:

Objective

Duchenne muscular dystrophy (DMD) is caused by the inability to produce dystrophin protein at the myofiber membrane. A method to rescue dystrophin production by antisense oligonucleotides, termed exon-skipping, has been reported for the mdx mouse and in four DMD patients by local intramuscular injection. We sought to test efficacy and toxicity of intravenous oligonucleotide (morpholino)-induced exon skipping in the DMD dog model.

Methods

We tested a series of antisense drugs singly and as cocktails, both in primary cell culture, and two in vivo delivery methods (intramuscular injection and systemic intravenous injection). The efficiency and efficacy of multiexon skipping (exons 6-9) were tested at the messenger RNA, protein, histological, and clinical levels.

Re

SUBMITTER: Yokota T 

PROVIDER: S-EPMC5951302 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature