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J. Pers. Med. 2018, 8(4), 38; https://doi.org/10.3390/jpm8040038

Applications of CRISPR/Cas9 for the Treatment of Duchenne Muscular Dystrophy

1
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, 8812-112 St., Edmonton, AB T6G 2H7, Canada
2
The Friends of Garret Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, 8812-112 St., Edmonton, AB T6G 2H7, Canada
These authors contributed equally to the work.
*
Author to whom correspondence should be addressed.
Received: 31 October 2018 / Revised: 20 November 2018 / Accepted: 20 November 2018 / Published: 24 November 2018
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Abstract

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein that leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed. View Full-Text
Keywords: Duchenne muscular dystrophy (DMD); CRISPR/Cas9; exon skipping therapy; gene editing; human induced pluripotent stem cells (hiPSCs); immortalized patient muscle cells; mdx mice; humanized dystrophic mouse models; deltaE50-MD dog model Duchenne muscular dystrophy (DMD); CRISPR/Cas9; exon skipping therapy; gene editing; human induced pluripotent stem cells (hiPSCs); immortalized patient muscle cells; mdx mice; humanized dystrophic mouse models; deltaE50-MD dog model
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Lim, K.R.Q.; Yoon, C.; Yokota, T. Applications of CRISPR/Cas9 for the Treatment of Duchenne Muscular Dystrophy. J. Pers. Med. 2018, 8, 38.

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