| Autor: |
Thi Thanh Huong Le, Ngoc Tung Tran, Thi Mai Lan Dao, Dinh Dung Nguyen, Huy Duong Do, Thi Lien Ha, Ralf Kühn, Thanh Liem Nguyen, Klaus Rajewsky, Van Trung Chu |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Frontiers in Genetics, Vol 10 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1664-8021 |
| DOI: |
10.3389/fgene.2019.00625 |
| Popis: |
Patients with Rett syndrome (RTT) have severe mental and physical disabilities. The majority of RTT patients carry a heterozygous mutation in methyl-CpG binding protein 2 (MECP2), an X-linked gene encoding an epigenetic factor crucial for normal nerve cell function. No curative therapy for RTT syndrome exists, and cellular mechanisms are incompletely understood. Here, we developed a CRISPR/Cas9-mediated system that targets and corrects the disease relevant regions of the MECP2 exon 4 coding sequence. We achieved homologous recombination (HR) efficiencies of 20% to 30% in human cell lines and iPSCs. Furthermore, we successfully introduced a MECP2R270X mutation into the MECP2 gene in human induced pluripotent stem cells (iPSCs). Consequently, using CRISPR/Cas9, we were able to repair such mutations with high efficiency in human mutant iPSCs. In summary, we provide a new strategy for MECP2 gene targeting that can be potentially translated into gene therapy or for iPSCs-based disease modeling of RTT syndrome. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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