Objective 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. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineophthalmologynatural sciencesbiological sciencesgeneticsgenomesmedical and health sciencesmedical biotechnologycells technologies Keywords retina AAV inherited retinal degenerations Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-ADG-2015 - ERC Advanced Grant Call for proposal ERC-2015-AdG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution FONDAZIONE TELETHON ETS Net EU contribution € 2 314 314,50 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 Total cost € 2 364 314,50 Beneficiaries (3) Sort alphabetically Sort by Net EU contribution Expand all Collapse all FONDAZIONE TELETHON ETS Italy Net EU contribution € 2 314 314,50 Address VIA VARESE 16/B 00185 Roma 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 Total cost € 2 364 314,50 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 € 50 000,00 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 Total cost € 50 000,00 UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II Italy Net EU contribution € 135 249,50 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 Total cost € 135 249,50