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Genome Editing for Neuromuscular Diseases

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Genome Editing

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB))

Abstract

Neuromuscular diseases are a diverse range of conditions that include myopathic and neuropathic disorders related to muscular dysfunction. Inherited neuromuscular diseases are the result of a broad spectrum of genetic mutations, including point mutations, insertions and deletions, chromosomal rearrangements, epigenetic aberrations, and repeat expansions or contractions. Targeted genome editing is a promising method to correct the inherited mutations underlying these disorders. Over the last decade there have been many significant advances in engineering targeted DNA-binding proteins to manipulate specific sequences of complex genomes. These genome editing tools are rapidly becoming viable therapeutics that will allow the targeted addition, exchange, or removal of almost any genetic sequence in the human genome. In this chapter, selected neuromuscular diseases representing inherited myopathies or neuropathies are discussed. The genome editing tools available to create targeted genetic modifications are reviewed. Promising cell- and gene-based therapies are introduced in the context of the treatment of neuromuscular disorders in combination with genome editing therapies. Finally, specific examples of how genome editing may be applied to correct the genetic basis of particular neuromuscular disorders are presented and discussed.

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Abbreviations

AAV:

Adeno-associated virus

BMD:

BECKER muscular dystrophy

CRISPR:

Clustered regularly interspaced short palindromic repeats

DM:

Myotonic dystrophy

DMD:

Duchenne muscular dystrophy

DSB:

Double-strand break

FSHD:

Fascioscapulohumeral dystrophy

gRNA:

Guide RNA

HDR:

Homology-directed repair

HT:

Huntington’s disease

iPSC:

Induced pluripotent stem cell

LGMD2B:

Limb-girdle muscular dystrophy type 2B

MGN:

Meganuclease

MM:

Miyoshi myopathy

NHEJ:

Non-homologous end joining

RVD:

Repeat variable diresidue

SMA:

Spinal muscular atrophy

ssODN:

Single-strand oligodeoxynucleotide

TALEN:

Transcription activator-like effector nuclease

ZFN:

Zinc finger nuclease

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  1. Department of Biomedical Engineering, Duke University, Room 136 Hudson Hall, 90281, Durham, NC, 27708-0281, USA

    David G. Ousterout Ph.D. & Charles A. Gersbach Ph.D.

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  2. Charles A. Gersbach Ph.D.
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  1. Inst for Cell & Gene Therapy, Universitaetsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany

    Toni Cathomen

  2. University of North Carolina, Chapel Hill, North Carolina, USA

    Matthew Hirsch

  3. Stanford Medical School, Palo Alto, California, USA

    Matthew Porteus

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Ousterout, D.G., Gersbach, C.A. (2016). Genome Editing for Neuromuscular Diseases. In: Cathomen, T., Hirsch, M., Porteus, M. (eds) Genome Editing. Advances in Experimental Medicine and Biology(). Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3509-3_4

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