Objectif The project aims to develop a gene therapy technology model based on autologous transplantation of skin made in vitro from genetically modified epidermal stem cells. This includes developing vectors, gene transfer technology, and preclinical models of gene therapy of rare inherited defects treatable with local delivery of a recombinant protein. The research focuses on dystrophic epidermolysis bullosa (DEB), a rare, disabling skin disease caused by inherited defects of collagen type VII. The workplan consists in: - Recruiting, genotyping and characterizing at molecular level cohorts of patients with recessive and dominant DEB - Isolating epithelial stem cells from the skin of DEB patients and DEB dogs, a spontaneous large animal model for the disease - Developing viral vectors (oncoretroviral, lentiviral, and hybrid adeno/AAV vectors) to integrate and stably express the collagen VII cDNA in DEB epidermal stem cells ex vivo - Transducing highly clonogenic DEB keratinocytes with the most appropriate vector(s) - constructing skin equivalents made with genetically corrected DEB cells to assess the full morphological and functional reversion of the DEB phenotype - Constructing transplantable epithelia using genetically corrected DEB cells and preclinical assessment of their performance in vivo in appropriate immune competent animal models - Developing a technology for production and downstream processing of clinical-grade viral vectors preparations under GMP/GLP standards -Establishing SOP, protocols and guidelines to genetically modify epidermal stem cells used to produce skin implants for clinical use- Disseminating results. The project's immediate goal is to develop a gene therapy approach to DEB and design appropriate phase I/II clinical trials to exploit the knowledge generated. This research ultimately targets the implementation of a technology applicable to other genetic protein deficiencies requiring local or systemic delivery of active molecules. Champ scientifique medical and health sciencesclinical medicineoncologyskin cancermedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinetransplantationmedical and health sciencesmedical biotechnologyimplants Mots‑clés Keratinocyte blistering disease collagenVII transplantable epithelium Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Thème(s) LIFESCIHEALTH-1.2.4 - Development and testing of new preventive and therapeutic tools, such a somatic gene and cell therapies (in particular stem cell therapies, for example those on neurological and neuromuscular disorders) and immunotherapies LSH-2003-1.2.4-8 - Use of gene transfer for curative therapy of human skin disease Appel à propositions FP6-2003-LIFESCIHEALTH-I Voir d’autres projets de cet appel Régime de financement NoE - Network of Excellence Coordinateur INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE Contribution de l’UE Aucune donnée Adresse 101 rue de Tolbiac PARIS France Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée Participants (7) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire FONDAZIONE BANCA DEGLI OCCHI DEL VENETO O.N.L.U.S. Italie Contribution de l’UE Aucune donnée Adresse via Felisati 109 VENEZIA-MESTRE Voir sur la carte Coût total Aucune donnée UNIVERSITA' DI MODENA E REGGIO EMILIA Italie Contribution de l’UE Aucune donnée Adresse VIA UNIVERSITA', 4 MODENA Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée UNIVERSITAETSKLINIK FREIBURG Allemagne Contribution de l’UE Aucune donnée Adresse Hugstetter Strasse 49 FREIBURG Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée CENTRO DE INVESTIGACIONES ENERGÉTICAS MEDIOAMBIENTALES Y TECNOLÓGICAS Espagne Contribution de l’UE Aucune donnée Adresse Avda Complutense 22 MADRID Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée MOLECULAR MEDICINE S.P.A. Italie Contribution de l’UE Aucune donnée Adresse Via Olgettina 58 MILANO Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée DEBRA EUROPE Royaume-Uni Contribution de l’UE Aucune donnée Adresse DebRA House, 13 Wellington Business Park, Dukes Ride CROWTHORNE Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée INSERM TRANSFERT SA France Contribution de l’UE Aucune donnée Adresse 7 rue Watt PARIS 13 Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée
