Objective 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. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Programme(s) FP7-HEALTH - Specific Programme "Cooperation": Health Topic(s) HEALTH.2013.0-1 - Boosting the translation of health research projects' results into innovative applications for health Call for proposal FP7-HEALTH-2013-INNOVATION-2 See other projects for this call Funding Scheme CP-FP - Small or medium-scale focused research project Coordinator UNIVERSITA VITA-SALUTE SAN RAFFAELE EU contribution € 2 050 575,30 Address VIA OLGETTINA 58 20132 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments Administrative Contact Maria Rosa Pedrazzi (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS Netherlands EU contribution € 573 744,00 Address PLESMANLAAN 121 1066 CX Amsterdam See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Research Organisations Administrative Contact Henri Van Luenen (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Germany EU contribution € 478 126,00 Address IM NEUENHEIMER FELD 280 69120 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Administrative Contact Ina Krischek (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSITY COLLEGE LONDON EU contribution € 478 125,00 Address GOWER STREET WC1E 6BT LONDON See on map Activity type Higher or Secondary Education Establishments Administrative Contact Malgorzata Kielbasa (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data AGC BIOLOGICS SPA Italy EU contribution € 2 419 426,70 Address VIA MEUCCI, 3 20091 BRESSO MI See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Enrico Cappelli (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data