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Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review.
JAMA Neurol. 2016 Nov 01; 73(11):1349-1355.JN

Abstract

Importance

Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1.

Objectives

To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing.

Evidence Review

PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed.

Findings

Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models.

Conclusions and Relevance

Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies.

Authors+Show Affiliations

Department of Molecular Biology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center and Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas.Department of Molecular Biology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center and Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas.Department of Molecular Biology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center and Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas.Department of Molecular Biology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center and Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas.

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

27668807

Citation

Long, Chengzu, et al. "Genome Editing of Monogenic Neuromuscular Diseases: a Systematic Review." JAMA Neurology, vol. 73, no. 11, 2016, pp. 1349-1355.
Long C, Amoasii L, Bassel-Duby R, et al. Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review. JAMA Neurol. 2016;73(11):1349-1355.
Long, C., Amoasii, L., Bassel-Duby, R., & Olson, E. N. (2016). Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review. JAMA Neurology, 73(11), 1349-1355. https://doi.org/10.1001/jamaneurol.2016.3388
Long C, et al. Genome Editing of Monogenic Neuromuscular Diseases: a Systematic Review. JAMA Neurol. 2016 Nov 1;73(11):1349-1355. PubMed PMID: 27668807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review. AU - Long,Chengzu, AU - Amoasii,Leonela, AU - Bassel-Duby,Rhonda, AU - Olson,Eric N, PY - 2016/9/27/pubmed PY - 2017/5/30/medline PY - 2016/9/27/entrez SP - 1349 EP - 1355 JF - JAMA neurology JO - JAMA Neurol VL - 73 IS - 11 N2 - Importance: Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. Objectives: To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. Evidence Review: PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Findings: Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. Conclusions and Relevance: Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/27668807/Genome_Editing_of_Monogenic_Neuromuscular_Diseases:_A_Systematic_Review_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2016.3388 DB - PRIME DP - Unbound Medicine ER -