Project description DEENESFRITPL Novel adeno-associated vectors for liver gene transfer Recombinant adeno-associated vectors (AAV) achieved remarkable success in recent clinical trials for liver gene transfer. However, several hurdles prevent expansion of AAV-mediated therapy to all patients, including transient AAV-mediated expression in proliferating hepatocytes due to episomal AAV genome dilution, hepatotoxicity and immune response against AAVs, and pre-existing immunity to AAV capsids. The EU-funded AAVolution project proposes to find novel small Cas nucleases for in vivo AAV-mediated genome editing with self-replicating episomal AAVs. The aim is to avoid transgene dilution, create synthetic AAVs with reduced toxicity and develop technologies to overcome pre-existing immunity to AAVs. The novel tool set will enable broad expansion of AAV-mediated gene therapy for indications beyond rare diseases. Show the project objective Hide the project objective Objective Liver-directed gene therapy has undergone significant development in the last two decades. Recombinant adeno-associated vectors (AAV) are the vectors of choice for liver gene transfer and have recently achieved remarkable successes in clinical trials. However, there are still large groups of patients who have limited access to therapy. The major hurdles toward expanding the indication of AAV-mediated liver gene therapy are: i) transient AAV-mediated expression in proliferating hepatocytes, i.e. newborn or regenerating livers, due to dilution of episomal AAV genome in proliferating cells; ii) dose-dependent hepatotoxicity and immune response against AAVs; and iii) pre-existing immunity to AAV capsids, which currently preclude its systemic delivery in about 50% of individuals. AAVolution gathers renowned European experts in the field of AAV vectorology, gene therapy, genome editing and immunology, with the ambitious goal to develop and implement innovative therapeutic tools to effectively address these challenges. To this aim AAVolution proposes: i) to seek novel small Cas nucleases for in vivo AAV-mediated genome editing ii)to develop self-replicating episomal AAVs to avoid transgene dilution in proliferating livers; iii) to generate synthetic AAVs characterized by enhanced potency and reduced toxicity, by screening of novel AAV capsid libraries; iv) and to develop improved technologies to overcome pre-existing immunity to AAVs by transiently reducing the levels of circulating anti-AAV neutralizing antibodies.AAVolution will significantly expand the toolkit for AAV-mediated liver gene therapy, developing novel and improved molecular instruments to address the most relevant hurdles toward safer and more effective therapies, and provide access to treatment to patients that are currently excluded from clinical trials. Moreover, these novel tools will constitute an innovative platform with a potential for broad expansion of disease indications beyond the rare diseases. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsgenomes Programme(s) HORIZON.3.1 - The European Innovation Council (EIC) Main Programme Topic(s) HORIZON-EIC-2021-PATHFINDERCHALLENGES-01-03 - Emerging Technologies in Cell and Gene therapy Call for proposal HORIZON-EIC-2021-PATHFINDERCHALLENGES-01 See other projects for this call Funding Scheme HORIZON-AG - HORIZON Action Grant Budget-Based Coordinator FONDAZIONE TELETHON ETS Net EU contribution € 1 087 600,00 Address Via varese 16/b 00185 Roma Italy See on map Region Centro (IT) Lazio Roma Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Participants (8) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. INNOVAVECTOR SRL Italy Net EU contribution € 40 000,00 Address Via campi flegrei 34 80078 Pozzuoli See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Sud Campania Napoli Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. NEXT GENERATION DIAGNOSTIC SRL Italy Net EU contribution € 15 000,00 Address Via campi flegrei 34 80078 Pozzuoli See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Sud Campania Napoli Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 ASSOCIATION GENETHON France Net EU contribution € 591 000,00 Address Rue de l internationale 1 bis 91002 Evry See on map Region Ile-de-France Ile-de-France Essonne Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITA DEGLI STUDI DI TRENTO Italy Net EU contribution € 551 600,00 Address Via calepina 14 38122 Trento See on map Region Nord-Est Provincia Autonoma di Trento Trento Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA Spain Net EU contribution € 551 600,00 Address Avenida de pio xii 55 31008 Pamplona See on map Region Noreste Comunidad Foral de Navarra Navarra Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 MEDIZINISCHE HOCHSCHULE HANNOVER Germany Net EU contribution € 512 200,00 Address Carl-neuberg-strasse 1 30625 Hannover See on map Region Niedersachsen Hannover Region Hannover Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 CINFERENCE UG Germany Net EU contribution € 257 000,00 Address Rheinsberger strasse 76/77 c/o fact 10115 Berlin See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Berlin Berlin Berlin Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II Italy Net EU contribution € 394 000,00 Address Corso umberto i, 40 80138 Napoli See on map Region Sud Campania Napoli Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
