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Antisense-mediated exon skipping for Duchenne muscular dystrophy
Development of an antisense-mediated exon skipping therapy for Duchenne muscular dystrophy Making sense out of nonsense
Engels
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Duchenne muscular dystrophy (DMD) is a severe, §progressive muscle wasting disease for which there §is currently no cure. The disease is caused by §mutations in the DMD gene that completely abolish §the function of the protein dystrophin. §This thesis focuses on the development of a §promising new therapy, so called antisense-mediated §exon skipping, that aims to restore the disrupted §dystrophin reading frame to allow generation of §internally deleted, but partly functional dystrophin §proteins, as found in the less severe Becker §muscular dystrophy.§The thesis describes the DMD gene, the dystrophin §protein, diseases associated with mutations in the §DMD gene and animal models. It provides an overview §of potential therapies for Duchenne muscular §dystrophy and describes how antisense-mediated §modulation of splicing can be used for other §therapeutic and research purposes. Finally it gives §a detailed overview of the rationale and the §development of the exon skipping therapy for §Duchenne muscular dystrophy.
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