Project description DEENESFRITPL AI-assisted target discovery for anticancer immunotherapy The subtype of endothelial cells (EC) with immunomodulatory gene signatures (IMECs) is important for alternative immunotherapy development. The silencing of IMEC immunosuppressive genes provides opportunities to improve efficacy and overcome resistance in anticancer immunotherapy. The EU funded MystIMEC project aims to validate 50 EC targets and patent 5 new targets for alternative IMEC based immunotherapy. The project will capitalise on a previously developed AI-based tool to predict new immunosuppressive functions for endothelial genes and a proprietary technology that enables the efficient generation of EC-specific knockout mice to validate the new targets. Show the project objective Hide the project objective Objective Compared to my previous Advanced ERC grants, this proposal is fundamentally different not only concerning its topic but also regarding its ambition to offer greater societal impact by coupling knowledge gain tighter to translation. It promises to obtain new insights in an understudied endothelial cell (EC) subtype with immunomodulatory gene signatures (coined “IMECs”), highly relevant for alternative immunotherapy development. Indeed, silencing immunosuppressive genes in IMECs offers unprece-dented opportunities to improve the efficacy of and to overcome the resistance to current anti-cancer immunotherapy, to which the immunosuppressive tumor endothelium contributes. To identify previously unknown/unmined (“virgin”) drug targets, we also focus on “mystery” genes, lacking func-tional annotation / PubMed reports (comprising 30% of the human coding genome). We developed: (i) an innovative artificial intelligence (AI)-based tool (SCMYSTERYDENTIFIER) to predict new immunosuppres-sive functions for endothelial “mystery” genes; and (ii) a revolutionizing (“REVOLT”) technology (based on injecting EC-selective lipid nanoparticles containing sgRNA in mice expressing Cas9 selectively in ECs) to generate EC-specific knockout mice rapidly (days)/inexpensively (300€/mouse) at an unprece-dented scale in order to validate these targets. Demystifying the mystery genome offers formidable opportunities for knowledge gain and therapy development. We will validate 50 new EC targets and aspire to identify and patent 5 previously unknown targets for alternative IMEC-based immunotherapy. The SCMYSTERYDENTIFIER tool can be made generic to discover any type of function for mystery genes in any cell type, while the REVOLT technology promises to revolutionize the pace of genetic research in the vascular biology field, offering formidable impact for the research community in academia and pharma. Fields of science natural sciencescomputer and information sciencesartificial intelligencenatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsengineering and technologynanotechnologynano-materialsmedical and health sciencesbasic medicineimmunologyimmunotherapynatural sciencesbiological sciencesgeneticsgenomes Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2021-ADG - ERC ADVANCED GRANTS Call for proposal ERC-2021-ADG See other projects for this call Funding Scheme HORIZON-AG - HORIZON Action Grant Budget-Based Coordinator VIB VZW Net EU contribution € 3 498 426,00 Address Rijvisschestraat 120 9052 Zwijnaarde - gent Belgium See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent 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
