Abstract
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene. Most deletions, duplications, or indels lead to shift of mRNA reading frame, which prevent the production of dystrophin protein. DMD is the leading fatal genetic disorder in childhood. One therapeutic strategy aims to skip one or more exons to restore reading frame to enable the production of internally truncated proteins with partial functionality. However, to date the efficiency of this strategy is suboptimal. Here we present methods for assessing exon skipping using AON alone or in combination with skip booster in the context of human DMD patient fibroblast derived myotubes and in the mdx mouse model of DMD.
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Acknowledgments
F.B. has received a postdoc fellowship grant from the UCLA Center for Duchenne Muscular Dystrophy-NIH NIAMS U54 AR052646 Wellstone Center of Excellence Training Fellowship. This work was funded from grants from the NIH (1T32AR65972A1) and the California Institute of Regenerative Medicine (TRX-05426). Support for the research was also provided by the UCLA Muscular Dystrophy Core Center (NIH grant 5P30AR057230) within the Center for Duchenne Muscular Dystrophy at UCLA. Competing interests: S.F.N. and M.C.M. are inventors on a pending patent on identification of small molecules that enhance exon skipping, filed by UCLA.
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Barthelemy, F., Wang, D., Nelson, S.F., Miceli, M.C. (2018). Validation and Detection of Exon Skipping Boosters in DMD Patient Cell Models and mdx Mouse. In: Yokota, T., Maruyama, R. (eds) Exon Skipping and Inclusion Therapies. Methods in Molecular Biology, vol 1828. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8651-4_19
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DOI: https://doi.org/10.1007/978-1-4939-8651-4_19
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