Objetivo 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. Ámbito científico medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesmicrobiologyvirologymedical and health sciencesbasic medicineimmunology Programa(s) 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) Tema(s) ERC-CG-2013-LS6 - ERC Consolidator Grant - Immunity and Infection Convocatoria de propuestas ERC-2013-CoG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-CG - ERC Consolidator Grants Institución de acogida ASSOCIATION GENETHON Aportación de la UE € 809 600,00 Dirección RUE DE L INTERNATIONALE 1 BIS 91002 Evry Francia Ver en el mapa Región Ile-de-France Ile-de-France Essonne Tipo de actividad Research Organisations Investigador principal Federico Mingozzi (Dr.) Contacto administrativo Séverine Pouillot (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (3) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo ASSOCIATION GENETHON Francia Aportación de la UE € 809 600,00 Dirección RUE DE L INTERNATIONALE 1 BIS 91002 Evry Ver en el mapa Región Ile-de-France Ile-de-France Essonne Tipo de actividad Research Organisations Investigador principal Federico Mingozzi (Dr.) Contacto administrativo Séverine Pouillot (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 La participación finalizó Francia Aportación de la UE Sin datos Dirección Place Jussieu 4 75252 PARIS Ver en el mapa Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Lucie Salvaudon (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos SORBONNE UNIVERSITE Francia Aportación de la UE € 1 921 200,00 Dirección 21 RUE DE L'ECOLE DE MEDECINE 75006 Paris Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Lucie Salvaudon (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
