Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5649549 | Journal of Investigative Dermatology | 2017 | 25 Pages |
Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects in type-VII collagen (C7), a protein encoded by the COL7A1 gene and essential for anchoring fibril formation at the dermal-epidermal junction. Gene therapy of RDEB is based on transplantation of autologous epidermal grafts generated from gene-corrected keratinocytes sustaining C7 deposition at the dermal-epidermal junction. Transfer of the COL7A1 gene is complicated by its very large size and repetitive sequence. This article reports a gene delivery approach based on the Sleeping beauty transposon, which allows integration of a full-length COL7A1 cDNA and secretion of C7 at physiological levels in RDEB keratinocytes without rearrangements or detrimental effects on their clonogenic potential. Skin equivalents derived from gene-corrected RDEB keratinocytes were tested in a validated preclinical model of xenotransplantation on immunodeficient mice, where they showed normal deposition of C7 at the dermal-epidermal junction and restoration of skin adhesion properties. These results indicate the feasibility and efficacy of a transposon-based gene therapy approach to RDEB.
Keywords
Related Topics
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Medicine and Dentistry
Dermatology
Authors
Maria Carmela Latella, Fabienne Cocchiarella, Laura De Rosa, Giandomenico Turchiano, Manuel A.F.V. Gonçalves, Fernando Larcher, Michele De Luca, Alessandra Recchia,