splicing (eukaryotic pre-mRNA processing) forum: topic
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Splicing for muscular dystrophy: toward Morpholino therapeutics
Jon Moulton
Tuesday, 08 July 2008 22:02 UTC
Morpholino antisense oligos can redirect splicing of pre-mRNA. This strategy is being used in development of therapeutic oligos for Duchenne muscular dystrophy. Here are a few references.
Papers
Vitiello L, Bassi N, Campagnolo P, Zaccariotto E, Occhi G, Malerba A, Pigozzo S, Reggiani C, Ausoni S, Zaglia T, Gamba P, Baroni MD, Ditadi AP. In vivo delivery of naked antisense oligos in aged mdx mice: Analysis of dystrophin restoration in skeletal and cardiac muscle. Neuromuscul Disord. 2008 Jul 2. [Epub ahead of print]
Jearawiriyapaisarn N, Moulton HM, Buckley B, Roberts J, Sazani P, Fucharoen S, Iversen PL, Kole R. Sustained Dystrophin Expression Induced by Peptide-conjugated Morpholino Oligomers in the Muscles of mdx Mice. Mol Ther. 2008 Jun 10. [Epub ahead of print]
Moulton HM, Fletcher S, Neuman BW, McClorey G, Stein DA, Abes S, Wilton SD, Buchmeier MJ, Lebleu B, Iversen PL. Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo. Biochem Soc Trans. 2007 Aug;35(Pt 4):826-8.
McClorey G, Fall AM, Moulton HM, Iversen PL, Rasko JE, Ryan M, Fletcher S, Wilton SD. Induced dystrophin exon skipping in human muscle explants. Neuromuscul Disord. 2006 Oct;16(9-10):583-90. Epub 2006 Aug 21
McClorey G, Moulton HM, Iversen PL, Fletcher S, Wilton SD. Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD. Gene Ther. 2006 Oct;13(19):1373-81. Epub 2006 May 25
Clinical trial
http://clinicaltrials.gov/ct2/show/NCT00159250
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