Cel 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. Dziedzina nauki medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesmicrobiologyvirologymedical and health sciencesbasic medicineimmunology Program(-y) 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) Temat(-y) ERC-CG-2013-LS6 - ERC Consolidator Grant - Immunity and Infection Zaproszenie do składania wniosków ERC-2013-CoG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-CG - ERC Consolidator Grants Instytucja przyjmująca ASSOCIATION GENETHON Wkład UE € 809 600,00 Adres RUE DE L INTERNATIONALE 1 BIS 91002 Evry Francja Zobacz na mapie Region Ile-de-France Ile-de-France Essonne Rodzaj działalności Research Organisations Kierownik naukowy Federico Mingozzi (Dr.) Kontakt administracyjny Séverine Pouillot (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (3) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko ASSOCIATION GENETHON Francja Wkład UE € 809 600,00 Adres RUE DE L INTERNATIONALE 1 BIS 91002 Evry Zobacz na mapie Region Ile-de-France Ile-de-France Essonne Rodzaj działalności Research Organisations Kierownik naukowy Federico Mingozzi (Dr.) Kontakt administracyjny Séverine Pouillot (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 Zakończenie uczestnictwa Francja Wkład UE Brak danych Adres Place Jussieu 4 75252 PARIS Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Lucie Salvaudon (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych SORBONNE UNIVERSITE Francja Wkład UE € 1 921 200,00 Adres 21 RUE DE L'ECOLE DE MEDECINE 75006 Paris Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Lucie Salvaudon (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych