Objectif Inherited retinal degenerations (IRDs) are a major cause of blindness worldwide. IRD patients witness inexorable progressive vision loss as no therapy is currently available. In the last decade my group has significantly contributed to a change of this scenario by developing efficient adeno-associated viral (AAV) vectors for retinal gene therapy that are safe and effective in humans. The objective of EYEGET (EYE GEne Therapy) is to overcome some of the current major limitations in the field of retinal gene therapy to expand initial therapeutic successes to a larger number of IRDs. To achieve this, we propose to use four parallel, highly innovative and complementary approaches: i. expansion of the limited AAV cargo capacity by a novel methodology based on co-administration of multiple AAVs that reassemble in target retinal cells and reconstitute large genes; ii. targeting of frequent dominant gain-of-function mutations that cause RP using state-of-the-art AAV-mediated genome editing technologies; iii. induction of retinal cells clearance of toxic IRD products by AAV-mediated activation of autophagy and lysosomal function; iv. development of methodologies to directly convert fibroblasts to photoreceptors that can be transplanted in retinas from IRD patients with advanced PR loss and for whom in vivo gene therapy is no longer an option. We will use a combination of in vitro and in vivo state-of-the-art technologies including novel AAV vector design, high content screening of drugs that enhance AAV transduction, genome editing, and advanced in vivo retinal phenotyping to obtain proof-of-concept for each of these therapeutic strategies. The results from this study may impact the quality of life of millions of people worldwide by providing a cure based on gene and/or cell therapy for a large group of IRDs. Champ scientifique medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineophthalmologynatural sciencesbiological sciencesgeneticsgenomesmedical and health sciencesmedical biotechnologycells technologies Mots‑clés retina AAV inherited retinal degenerations Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-ADG-2015 - ERC Advanced Grant Appel à propositions ERC-2015-AdG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil FONDAZIONE TELETHON ETS Contribution nette de l'UE € 2 314 314,50 Adresse VIA VARESE 16/B 00185 Roma Italie Voir sur la carte Région Centro (IT) Lazio Roma Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 364 314,50 Bénéficiaires (3) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire FONDAZIONE TELETHON ETS Italie Contribution nette de l'UE € 2 314 314,50 Adresse VIA VARESE 16/B 00185 Roma Voir sur la carte Région Centro (IT) Lazio Roma Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 364 314,50 Tiers Entité juridique autre qu’un sous-traitant qui est affiliée ou juridiquement liée à un participant. L’entité réalise des travaux dans les conditions prévues par la convention de subvention, fournit des biens ou des services pour l’action, mais n’a pas signé la convention de subvention. Le tiers respecte les règles applicables au participant qui lui est lié dans le cadre de la convention de subvention en ce qui concerne l’éligibilité des coûts et le contrôle des dépenses. INNOVAVECTOR SRL Italie Contribution nette de l'UE € 50 000,00 Adresse VIA CAMPI FLEGREI 34 80078 Pozzuoli Voir sur la carte PME L’entreprise s’est définie comme une PME (petite et moyenne entreprise) au moment de la signature de la convention de subvention. Oui Région Sud Campania Napoli Type d’activité Private for-profit entities (excluding Higher or Secondary Education Establishments) Liens Contacter l’organisation Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 50 000,00 UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II Italie Contribution nette de l'UE € 135 249,50 Adresse CORSO UMBERTO I, 40 80138 Napoli Voir sur la carte Région Sud Campania Napoli Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 135 249,50