Cel We aim to develop ex vivo gene therapy of recessive dystrophic epidermolysis bullosa RDEB. It is caused by loss of function mutations in the collagen VII gene (COL7A1) encoding anchoring fibrils. Patients suffer from skin blistering since birth, and from severe local and systemic complications resulting in poor prognosis. We lack a specific treatment for RDEB, but ex vivo gene transfer to epidermal stem cells shows therapeutic potential. in vitro correction of primary RDEB keratinocytes and fibroblasts by retroviral and lentiviral COL7A1 cDNA vectors was reported. Reports of leukemia caused by retroviral insertional mutagenesis in gene therapy of X-SCID steered us toward safer SIN vectors. In Step I of this project, we will design safe SIN retroviral and lentiviral COL7A1 vectors. Different promoters and viral envelope proteins will be tested for efficient gene delivery and expression in cultured primary keratinocytes and fibroblasts. We will study the proliferative capacity of transduced cells and assess long-term expression of recombinant collagen VII. We will analyse synthesis, folding and secretion of recombinant collagen VII, and its ability to form anchoring fibres in a skin equivalent model and in skin grafts on mice. Vectors will be structed and produced form to GLP standards. In Step II, cell clones producing the highest titres of the selected SIN retroviral or lentiviral vector (mini-cell bank) will be expanded, evaluated, and a unique GMP master cell bank will be established. This MCB will be tested for safety, to be used in the production of clinical grade viral particles. Step III will be a pilot clinical trial (Phase I/II) of genetically corrected autologous skin grafts in selected patients. This project, which combines the complementary expertise of several international groups, will serve as proof of principle for the treatment of RDEB, and as a model for the treatment of severe dermatological genetic disorders by ex vivo gene therapy. Dziedzina nauki medical and health sciencesclinical medicineoncologyskin cancermedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesbasic medicineimmunologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinesurgerysurgical procedures Słowa kluczowe Lentivirus Recessive Dystrophie Epidermolysis Bullosa Retrovirus Type VII collagen Program(-y) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Temat(-y) LSH-2003-1.2.4-8 - Use of gene transfer for curative therapy of human skin disease Zaproszenie do składania wniosków FP6-2003-LIFESCIHEALTH-I Zobacz inne projekty w ramach tego zaproszenia System finansowania STIP - Specific Targeted Innovation Project Koordynator INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Wkład UE Brak danych Adres 101 Rue de tolbiac PARIS Francja Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (8) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko ECOLE POLYTECHNIQUE FÉDÉRALE DE LAUSANNE Szwajcaria Wkład UE Brak danych Adres SV IGD LDCS Station 15 LAUSANNE Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS - HÔPITAL NECKER-ENFANTS MALADES Francja Wkład UE Brak danych Adres 3 avenue Victoria PARIS Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych GENETHON Francja Wkład UE Brak danych Adres 1 bis rue de l'internationale BP 60 EVRY Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych QUEEN MARY & WESTFIELD COLLEGE, UNIVERSITY OF LONDON Zjednoczone Królestwo Wkład UE Brak danych Adres Mile End Road LONDON Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych KINGS COLLEGE LONDON Zjednoczone Królestwo Wkład UE Brak danych Adres Strand LONDON Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych MAX PLANCK SOCIETY FOR THE ADVANCEMENT OF SCIENCES, REPRESENTED BY MPI OF BIOCHEMISTRY Niemcy Wkład UE Brak danych Adres Am Klopferspitz 18 MARTINSRIED Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych DEBRA EUROPE Zjednoczone Królestwo Wkład UE Brak danych Adres DEBRA House, 13 Wellington Business Park, Dukes Ride CROWTHORNE Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych INSERM-TRANSFERT SA Francja Wkład UE Brak danych Adres 101 Rue de tolbiac PARIS Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych
