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Muscle Gene Therapy pp 371–382Cite as

Alternate Translational Initiation of Dystrophin: A Novel Therapeutic Approach

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Abstract

A founder allele in the DMD gene results in a syndrome ranging from minimally symptomatic Becker muscular dystrophy to asymptomatic hyperCKemia via expression of a highly functional N-terminal deleted version of the dystrophin protein (the ΔCH1 isoform). Translation of this protein results from utilization of a recently discovered internal ribosome entry site (IRES) within exon 5. The IRES is not active in the presence of a duplication of exon 2—the most common single-exon duplication—but is active in its absence. We have developed an AAV-encapsidated U7snRNA vector that targets and induces skipping of exon 2, resulting in either expression of a wild-type dystrophin or of the ΔCH1 isoform, either of which is therapeutic.

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Author information

Authors and Affiliations

  1. The Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA

    Nicolas Wein & Kevin M. Flanigan

  2. Department of Pediatrics, The Ohio State University, Columbus, OH, USA

    Nicolas Wein & Kevin M. Flanigan

  3. Department of Neurology, The Ohio State University, Columbus, OH, USA

    Kevin M. Flanigan

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  1. Nicolas Wein
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  2. Kevin M. Flanigan
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Correspondence to Kevin M. Flanigan .

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Editors and Affiliations

  1. Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA, Department of Biomedical Sciences College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Department of Bioengineering, University of Missouri, Columbia, MO, USA

    Dongsheng Duan

  2. Department of Pediatrics Nationwide Children’s Hospital and Research Institute, Department of Neurology Nationwide Children’s Hospital and Research Institute, The Ohio State University, Columbus, OH, USA

    Jerry R. Mendell

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Wein, N., Flanigan, K.M. (2019). Alternate Translational Initiation of Dystrophin: A Novel Therapeutic Approach. In: Duan, D., Mendell, J. (eds) Muscle Gene Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-03095-7_21

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