Objetivo Substantial evidence supports the therapeutic potential of ex vivo gene therapy based on Hematopoietic Stem Cell (HSC) or T lymphocytes to treat inherited diseases or cancer. Yet, the intrinsic limitations of current gene replacement approaches based on semi-randomly integrating vectors, and the occurrence in some clinical trials of severe adverse events related to gene transfer, prevent safe deployment and broad application of gene therapy. This project aims to overcome these limits by exploiting the results of an earlier highly successful integrated project (PERSIST), which demonstrated the potential of gene targeting technologies based on engineered nucleases to provide radical new solutions to these hurdles. By homology-driven repair of a nuclease-targeted dysfunctional gene, we will insert a functional copy downstream its own endogenous promoter in HSC, thus restoring both function and physiological expression control. For adoptive T-cell therapy, we will combine nuclease-mediated disruption of the endogenous TCR genes with transfer of tumor-specific TCR, thus editing T-cell specificity at the genetic level. We will develop these innovative approaches into robust, scalable and clinically ready processes for safe ex vivo genetic modification of hematopoietic cells, and apply them to the treatment of paradigmatic diseases that provide a favourable risk-benefit ratio for clinical testing. Because both HSC and T-cell based gene therapy strategies share methodological aspects and technological challenges, we will address them systematically by involving a SME which holds unique know-how and top-level expertise in vector manufacturing and HSC and T-cell processing, as already established for our previous and ongoing gene therapy trials. Our findings will lead to the design of new clinical trials to provide durable benefits or even a cure to patients suffering from severe and otherwise fatal diseases, and representing a template for broaden application in medicine. Ámbito científico medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Programa(s) FP7-HEALTH - Specific Programme "Cooperation": Health Tema(s) HEALTH.2013.0-1 - Boosting the translation of health research projects' results into innovative applications for health Convocatoria de propuestas FP7-HEALTH-2013-INNOVATION-2 Consulte otros proyectos de esta convocatoria Régimen de financiación CP-FP - Small or medium-scale focused research project Coordinador UNIVERSITA VITA-SALUTE SAN RAFFAELE Aportación de la UE € 2 050 575,30 Dirección VIA OLGETTINA 58 20132 Milano Italia Ver en el mapa Región Nord-Ovest Lombardia Milano Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Maria Rosa Pedrazzi (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Participantes (4) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS Países Bajos Aportación de la UE € 573 744,00 Dirección PLESMANLAAN 121 1066 CX Amsterdam Ver en el mapa Región West-Nederland Noord-Holland Groot-Amsterdam Tipo de actividad Research Organisations Contacto administrativo Henri Van Luenen (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Alemania Aportación de la UE € 478 126,00 Dirección IM NEUENHEIMER FELD 280 69120 Heidelberg Ver en el mapa Región Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo de actividad Research Organisations Contacto administrativo Ina Krischek (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos UNIVERSITY COLLEGE LONDON Aportación de la UE € 478 125,00 Dirección GOWER STREET WC1E 6BT LONDON Ver en el mapa Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Malgorzata Kielbasa (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos AGC BIOLOGICS SPA Italia Aportación de la UE € 2 419 426,70 Dirección VIA MEUCCI, 3 20091 BRESSO MI Ver en el mapa Región Nord-Ovest Lombardia Milano Tipo de actividad Private for-profit entities (excluding Higher or Secondary Education Establishments) Contacto administrativo Enrico Cappelli (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos