Obiettivo Experience with adeno-associated virus (AAV) vector-mediated gene transfer in human trials has unveiled the therapeutic potential of this approach, with some of the most exciting results coming from clinical studies of gene transfer for hemophilia B, congenital blindness, and the recent market approval of the first AAV-based gene therapy in Europe. Follow-up data of subjects treated with AAV vectors is showing sustained correction of the disease phenotype for several years after gene transfer, and recent data confirmed that AAV vectors can drive expression of a transgene in humans for >10 years. With clinical development, however, some of the limitations of the approach, not entirely identified in preclinical studies, became obvious; in particular it is well established that the host immune system represents an important obstacle to be overcome in terms of both safety and efficacy of gene transfer in vivo with AAV vectors. The overall goal of this proposal is to gain critical, missing knowledge on the interactions between AAV vectors and the immune system in order to develop strategies to achieve safe, effective, and long-lasting gene transfer in humans.In this proposal we will: 1) Define the molecular signatures of the immune system in humans undergoing gene transfer with AAV vectors using cutting-edge, high-content immunophenotyping technologies; 2) Study the role of anti-AAV antibodies as determinants of AAV capsid immunogenicity using both in vitro and in vivo systems; 3) Identify novel pharmacological and cellular approaches to overcome T cell immunity to AAV; 4) Develop novel strategies to overcome pre-existing antibody responses to AAV.This proposal exploits the knowledge and the skills available in our lab to develop new tools and to provide novel, basic insights into the human immune responses to AAV that will have a direct impact on the quality of life of patients affected by inherited disorders. Campo scientifico medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesmicrobiologyvirologymedical and health sciencesbasic medicineimmunology Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-CG-2013-LS6 - ERC Consolidator Grant - Immunity and Infection Invito a presentare proposte ERC-2013-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-CG - ERC Consolidator Grants Istituzione ospitante ASSOCIATION GENETHON Contributo UE € 809 600,00 Indirizzo RUE DE L INTERNATIONALE 1 BIS 91002 Evry Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Essonne Tipo di attività Research Organisations Ricercatore principale Federico Mingozzi (Dr.) Contatto amministrativo Séverine Pouillot (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (3) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto ASSOCIATION GENETHON Francia Contributo UE € 809 600,00 Indirizzo RUE DE L INTERNATIONALE 1 BIS 91002 Evry Mostra sulla mappa Regione Ile-de-France Ile-de-France Essonne Tipo di attività Research Organisations Ricercatore principale Federico Mingozzi (Dr.) Contatto amministrativo Séverine Pouillot (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 Partecipazione conclusa Francia Contributo UE Nessun dato Indirizzo Place Jussieu 4 75252 PARIS Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Lucie Salvaudon (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato SORBONNE UNIVERSITE Francia Contributo UE € 1 921 200,00 Indirizzo 21 RUE DE L'ECOLE DE MEDECINE 75006 Paris Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Lucie Salvaudon (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
