Deletion of a Pathogenic Mutation-Containing Exon of COL7A1 Allows Clonal Gene Editing Correction of RDEB Patient Epidermal Stem Cells
نویسندگان
چکیده
1Epithelial Biomedicine Division, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; 2Department of Biomedical Engineering, Carlos III University (UC3M), Madrid, Spain; 3Institute of Pathology, Universitätsklinikum Heidelberg, Heidelberg, Germany; 4Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Spain; 5Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) U714, Madrid, Spain
منابع مشابه
Gene Editing for the Efficient Correction of a Recurrent COL7A1 Mutation in Recessive Dystrophic Epidermolysis Bullosa Keratinocytes
Clonal gene therapy protocols based on the precise manipulation of epidermal stem cells require highly efficient gene-editing molecular tools. We have combined adeno-associated virus (AAV)-mediated delivery of donor template DNA with transcription activator-like nucleases (TALE) expressed by adenoviral vectors to address the correction of the c.6527insC mutation in the COL7A1 gene, causing rece...
متن کاملHuman COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa.
Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide defi...
متن کاملType VII Collagen Gene Mutations (c.8569G>T and c.4879G>A) Result in the Moderately Severe Phenotype of Recessive Dystrophic Epidermolysis Bullosa in a Korean Patient
Dystrophic epidermolysis bullosa (DEB) are caused by mutations in the COL7A1 gene, which encodes type VII collagen. Even though more than 500 different COL7A1 mutations have been identified in DEB, it still remains to be under-investigated. To investigate the mutation of COL7A1 in moderately severe phenotype of recessive DEB (RDEB) in a Korean patient, the mutation detection strategy was consis...
متن کاملIdentification of a Novel Intragenic Deletion of the PHKD1 Gene in a Patient with Autosomal Recessive Polycystic Kidney Disease
Background Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1gene. In the present study, we describe a severe case of ARPKD carrying a point mutation and a novel four-exon deletion of PKHD1 gene. Materials and Methods The PKHD1, PKD1 and PKD2 ...
متن کاملPatient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa
Spontaneous reversion of disease-causing mutations has been observed in some genetic disorders. In our clinical observations of severe generalized recessive dystrophic epidermolysis bullosa (RDEB), a currently incurable blistering genodermatosis caused by loss-of-function mutations in COL7A1 that results in a deficit of type VII collagen (C7), we have observed patches of healthy-appearing skin ...
متن کامل