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 genecorrected 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.
Correction of recessive dystrophic epidermolysis bullosa by transposon-mediated integration of COL7A1 in transplantable patient-derived primary keratinocytes / Latella, Maria Carmela; Cocchiarella, Fabienne; De Rosa, Laura; Turchiano, Giandomenico; Gonçalves, Manuel; Larcher, Fernando; De Luca, Michele; Recchia, Alessandra. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - (2017), pp. 1-10.
Data di pubblicazione: | 2017 |
Data di prima pubblicazione: | 24-dic-2016 |
Titolo: | Correction of recessive dystrophic epidermolysis bullosa by transposon-mediated integration of COL7A1 in transplantable patient-derived primary keratinocytes. |
Autore/i: | Latella, Maria Carmela; Cocchiarella, Fabienne; De Rosa, Laura; Turchiano, Giandomenico; Gonçalves, Manuel; Larcher, Fernando; De Luca, Michele; Recchia, Alessandra |
Autore/i UNIMORE: | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.jid.2016.11.038 |
Rivista: | |
Pagina iniziale: | 1 |
Pagina finale: | 10 |
Codice identificativo ISI: | WOS:000396884400012 |
Codice identificativo Scopus: | 2-s2.0-85015969390 |
Codice identificativo Pubmed: | 28027893 |
Citazione: | Correction of recessive dystrophic epidermolysis bullosa by transposon-mediated integration of COL7A1 in transplantable patient-derived primary keratinocytes / Latella, Maria Carmela; Cocchiarella, Fabienne; De Rosa, Laura; Turchiano, Giandomenico; Gonçalves, Manuel; Larcher, Fernando; De Luca, Michele; Recchia, Alessandra. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - (2017), pp. 1-10. |
Tipologia | Articolo su rivista |
File in questo prodotto:
File | Descrizione | Tipologia | |
---|---|---|---|
latella et al.pdf | Versione dell'editore (versione pubblicata) | Administrator Richiedi una copia |

I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris