| RRC ID |
52186
|
| 著者 |
Zhang Y, Long C, Li H, McAnally JR, Baskin KK, Shelton JM, Bassel-Duby R, Olson EN.
|
| タイトル |
CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice.
|
| ジャーナル |
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.
|
| 巻・号 |
3(4)
|
| ページ |
e1602814
|
| 公開日 |
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
|
| 引用数 |
110
|
| リソース情報 |
| ヒト・動物細胞 |
HPS0164 |
