RRC ID 52186
Author Zhang Y, Long C, Li H, McAnally JR, Baskin KK, Shelton JM, Bassel-Duby R, Olson EN.
Title CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice.
Journal Sci Adv
Abstract Duchenne muscular dystrophy (DMD), caused by mutations in the X-linked dystrophin gene (DMD), is characterized by fatal degeneration of striated muscles. Dilated cardiomyopathy is one of the most common lethal features of the disease. We deployed Cpf1, a unique class 2 CRISPR (clustered regularly interspaced short palindromic repeats) effector, to correct DMD mutations in patient-derived induced pluripotent stem cells (iPSCs) and mdx mice, an animal model of DMD. Cpf1-mediated genomic editing of human iPSCs, either by skipping of an out-of-frame DMD exon or by correcting a nonsense mutation, restored dystrophin expression after differentiation to cardiomyocytes and enhanced contractile function. Similarly, pathophysiological hallmarks of muscular dystrophy were corrected in mdx mice following Cpf1-mediated germline editing. These findings are the first to show the efficiency of Cpf1-mediated correction of genetic mutations in human cells and an animal disease model and represent a significant step toward therapeutic translation of gene editing for correction of DMD.
Volume 3(4)
Pages e1602814
Published 2017-4-1
DOI 10.1126/sciadv.1602814
PII 1602814
PMID 28439558
PMC PMC5389745
MeSH Animals CRISPR-Cas Systems* Dystrophin* / genetics Dystrophin* / metabolism Humans Mice Mice, Inbred mdx Muscular Dystrophy, Animal / genetics Muscular Dystrophy, Animal / metabolism Muscular Dystrophy, Animal / pathology Muscular Dystrophy, Animal / therapy* Muscular Dystrophy, Duchenne / genetics Muscular Dystrophy, Duchenne / metabolism Muscular Dystrophy, Duchenne / pathology Muscular Dystrophy, Duchenne / therapy* Myocytes, Cardiac / metabolism* Myocytes, Cardiac / pathology
IF 13.117
Times Cited 110
Altmetric score
オルトメトリクス指標項目
The most frequently cited source X(Twitter)
Total number of mentions 305
Altmetric score changes over past 6months 3.0
Resource
Human and Animal Cells HPS0164