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RNAi Therapy for Dominant Muscular Dystrophies and Other Myopathies

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Muscle Gene Therapy

Abstract

Historically, the muscle gene therapy field has been primarily focused on replacing defective or missing genes underlying recessive disorders and has matured to the point where several gene replacement strategies have now been tested or are underway in human clinical trials. Unfortunately, gene replacement strategies are not indicated for treating dominant diseases, where reduction or elimination of an abnormal allele would be needed, and as a result, gene therapies for dominant muscular dystrophies have lagged behind. Importantly, the emergence of RNA interference (RNAi) as a gene-silencing tool provided a means to begin closing this development gap. In the first edition of this chapter of Muscle Gene Therapy, we discussed the prospects of combining RNAi and gene therapy to treat dominant muscle diseases, but proof of concept for its practical usage had not been demonstrated at the time. Here, in this second edition, we update our current understanding of the mechanisms underlying RNAi, compile several preclinical examples of RNAi-based gene therapies for muscle diseases, and discuss current prospects for translating these strategies toward the clinic.

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Author information

Authors and Affiliations

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

    Scott Q. Harper

  2. Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    Scott Q. Harper

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  1. Scott Q. Harper
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Correspondence to Scott Q. Harper .

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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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Harper, S.Q. (2019). RNAi Therapy for Dominant Muscular Dystrophies and Other Myopathies. In: Duan, D., Mendell, J. (eds) Muscle Gene Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-03095-7_28

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