Show simple item record

dc.contributor.authorLu, Qi Long
dc.contributor.authorMann, Christopher J
dc.contributor.authorLou, Fang
dc.contributor.authorBou-Gharios, George
dc.contributor.authorMorris, Glenn E
dc.contributor.authorXue, Shao-an
dc.contributor.authorFletcher, Sue
dc.contributor.authorPartridge, Terence A
dc.contributor.authorWilton, Stephen D
dc.identifier.citationLu , Q L , Mann , C J , Lou , F , Bou-Gharios , G , Morris , G E , Xue , S , Fletcher , S , Partridge , T A & Wilton , S D 2003 , ' Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse ' , Nature Medicine , vol. 9 , no. 8 , pp. 1009-14 .
dc.identifier.otherPURE: 308828
dc.identifier.otherPURE UUID: e18eefec-5967-42e3-b8c6-62032689c14d
dc.identifier.otherPubMed: 12847521
dc.identifier.otherScopus: 0042536463
dc.descriptionFull text of this article is not available in the UHRA
dc.description.abstractAs a target for gene therapy, Duchenne muscular dystrophy (DMD) presents many obstacles but also an unparalleled prospect for correction by alternative splicing. The majority of mutations in the dystrophin gene occur in the region encoding the spectrin-like central rod domain, which is largely dispensable. Thus, splicing around mutations can generate a shortened but in-frame transcript, permitting translation of a partially functional dystrophin protein. We have tested this idea in vivo in the mdx dystrophic mouse (carrying a mutation in exon 23 of the dystrophin gene) by combining a potent transfection protocol with a 2-O-methylated phosphorothioated antisense oligoribonucleotide (2OMeAO) designed to promote skipping of the mutated exon*. The treated mice show persistent production of dystrophin at normal levels in large numbers of muscle fibers and show functional improvement of the treated muscle. Repeated administration enhances dystrophin expression without eliciting immune responses. Our data establishes the realistic practicality of an approach that is applicable, in principle, to a majority of cases of severe dystrophinopathy.en
dc.relation.ispartofNature Medicine
dc.subjectGene Expression Regulation
dc.subjectGene Therapy
dc.subjectMice, Inbred mdx
dc.subjectMuscle, Skeletal
dc.subjectMuscular Dystrophy, Animal
dc.subjectMuscular Dystrophy, Duchenne
dc.subjectOligonucleotides, Antisense
dc.subjectRNA Splicing
dc.titleFunctional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouseen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record