Multiple exon skipping strategies to by-pass dystrophin mutations
نویسندگان
چکیده
منابع مشابه
Multiple exon skipping strategies to by-pass dystrophin mutations
Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy. Dystrophin mutations will require the removal of one or more exons to restore the reading frame and in some cases, multiple exon skipping strategies exist to restore dystrophin expression. However, for some small intra-exonic ...
متن کاملTargeted Exon Skipping to Address “Leaky” Mutations in the Dystrophin Gene
Protein-truncating mutations in the dystrophin gene lead to the progressive muscle wasting disorder Duchenne muscular dystrophy, whereas in-frame deletions typically manifest as the milder allelic condition, Becker muscular dystrophy. Antisense oligomer-induced exon skipping can modify dystrophin gene expression so that a disease-associated dystrophin pre-mRNA is processed into a Becker muscula...
متن کاملDeletion of Dystrophin In-Frame Exon 5 Leads to a Severe Phenotype: Guidance for Exon Skipping Strategies
Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin r...
متن کاملEffective Exon Skipping and Dystrophin Restoration by 2′-O-Methoxyethyl Antisense Oligonucleotide in Dystrophin-Deficient Mice
Antisense oligonucleotide (AO)-mediated exon-skipping therapy is one of the most promising therapeutic strategies for Duchenne Muscular Dystrophy (DMD) and several AO chemistries have been rigorously investigated. In this report, we focused on the effect of 2'-O-methoxyethyl oligonucleotides (MOE) on exon skipping in cultured mdx myoblasts and mice. Efficient dose-dependent skipping of targeted...
متن کاملMultiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion.
Deletion and duplication of one or more exons in the dystrophin gene account for 70% of patients with Duchenne and Becker muscular dystrophies (DMD and BMD) and other allelic clinical entities such as raised serum creatine kinase and X linked dilated cardiomyopathy (XLDC). The severity of the resulting phenotype can be generally predicted by whether these mutations lead to translation frame dis...
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ژورنال
عنوان ژورنال: Neuromuscular Disorders
سال: 2012
ISSN: 0960-8966
DOI: 10.1016/j.nmd.2011.10.007