期刊
MOLECULAR THERAPY
卷 29, 期 6, 页码 2008-2018出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2021.02.019
关键词
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资金
- Spanish grants from the Instituto de Salud Carlos III [PI17/01747, PI20/00615, AC17/00054, ER18TRL714]
- Ministry of Economy and Competitiveness [SAF2017-86810-R]
- European Regional Development Funds
- Avancell-CM grant [S2017/BMD-3692]
This study presents a gene-editing approach using CRISPR-Cas9 system to achieve gene correction in different cell types, showing therapeutic potential for RDEB.
Genome-editing technologies that enable the introduction of precise changes in DNA sequences have the potential to lead to a new class of treatments for genetic diseases. Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by extreme skin fragility. The recessive dystrophic subtype of EB (RDEB), which has one of the most severe phenotypes, is caused by mutations in COL7A1. In this study, we report a gene-editing approach for ex vivo homology-directed repair (HDR)-based gene correction that uses the CRISPR-Cas9 system delivered as a ribonucleoprotein (RNP) complex in combination with donor DNA templates delivered by adeno-associated viral vectors (AAVs). We demonstrate sufficient mutation correction frequencies to achieve therapeutic benefit in primary RDEB keratinocytes containing different COL7A1 mutations as well as efficient HDR-mediated COL7A1 modification in healthy cord blood-derived CD34(+) cells and mesenchymal stem cells (MSCs). These results are a proof of concept for HDR-mediated gene correction in different cell types with therapeutic potential for RDEB.
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