Chimeric snRNA molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin pre-mRNA induce exon skipping and restoration of a dystrophin synthesis in 48-50 DMD cells
نویسندگان
چکیده
*Institute Pasteur Fondazione Cenci-Bolognetti, Department of Genetics and Molecular Biology, University ‘‘La Sapienza,’’ P.le Aldo Moro 5, 00185 Rome, Italy; †Stem Cell Research Institute, Ospedale San Raffaele, 20132 Milan, Italy; §Department of Histology and Medical Embryology, University ‘‘La Sapienza,’’ 00161 Rome, Italy; and ‡Institute of Neurology, Catholic University and Centre for Neuromuscular Diseases, Unione Italiana Lotta alla Distrofia Muscolare–Rome Section, 00167 Rome, Italy
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Systemic Antisense Therapeutics for Dystrophin and Myostatin Exon Splice Modulation Improve Muscle Pathology of Adult mdx Mice
Antisense-mediated exon skipping is a promising approach for the treatment of Duchenne muscular dystrophy (DMD), a rare life-threatening genetic disease due to dystrophin deficiency. Such an approach can restore the disrupted reading frame of dystrophin pre-mRNA, generating a truncated form of the protein. Alternatively, antisense therapy can be used to induce destructive exon skipping of myost...
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Antisense oligonucleotides (AONs) in clinical development for Duchenne muscular dystrophy (DMD) aim to induce skipping of a specific exon of the dystrophin transcript during pre-mRNA splicing. This results in restoration of the open reading frame and consequently synthesis of a dystrophin protein with a shorter yet functional central rod domain. To monitor the molecular therapeutic effect of ex...
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Dystrophin deficiency, which leads to severe and progressive muscle degeneration in patients with Duchenne muscular dystrophy (DMD), is caused by frameshifting mutations in the dystrophin gene. A relatively new therapeutic strategy is based on antisense oligonucleotides (AONs) that induce the specific skipping of a single exon, such that the reading frame is restored. This allows the synthesis ...
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