論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 305 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | HPS0164 |