Descrizione del progetto
Un approccio avanzato di editing genico
Negli ultimi anni si sono registrati progressi nelle tecnologie di editing del genoma basate sul sistema CRISPR/Cas. Derivato dai meccanismi di difesa immunitaria dei batteri, il sistema utilizza molecole di RNA che legano la sequenza bersaglio e l’enzima Cas per scindere il DNA nel punto desiderato. Attualmente, il rilascio di questi componenti nelle cellule è mediato da vettori virali che, tuttavia, presentano un elevato rischio di tossicità. Finanziato dal Consiglio europeo per l’innovazione, il progetto EdiGenT introduce un sistema non virale basato su nanoparticelle con effetti collaterali minimi per il rilascio di componenti di editing genico nelle cellule. In combinazione con molecole avanzate di prime editor, garantisce la modifica del genoma senza le conseguenze dannose delle rotture del DNA a doppio filamento.
Obiettivo
Genome editing technologies based on CRISPR/Cas systems allow targeted genomic modification with unprecedented precision and have emerged as powerful alternatives to the conventional gene therapy approaches for various human diseases, with a series of clinical trials in progress. However, some crucial challenges remain to be addressed to enhance efficiency and safety and decrease costs of treatments.
Current viral-based delivery systems are associated with high risk of toxicity and immunogenicity and remain highly expensive. We will develop a new generation of non-viral delivery systems for gene editing tools based on the use of modified nanoparticles with human-derived protein moieties that will allow targeting the tissue and cells of interest in vivo with minimal adverse effects.
Prime editors have raised exciting possibilities for double-strand break free genome editing. However, a major limitation of current prime editors is highly variable efficiency both from one target to another and between cell types. We will design and evaluate novel prime editor tools in order to both increase activity per se and overcome cell-specific limitations.We will test our approach on the hematopoietic system to treat Sickle Cell Disease, avoiding the challenges and risks of hematopoietic stem cell manipulation associated with current gene therapy approaches, and thus providing a treatment much simpler, safer and cost-effective to implement.
Our technological breakthroughs address two key obstacles in cell and gene therapy: gene editing efficiency and systemic delivery. The novel prime editors and targeted nanoparticles that we will engineer will be combined to make unprecedented off-the-shelf, recombinant biologics for gene therapy. The versatility of the design of these novel recombinant biologics makes them suitable for the treatment of a vast majority of genetic diseases.
Campo scientifico
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- engineering and technologynanotechnologynano-materials
- natural sciencesmathematicspure mathematicsarithmeticsprime numbers
- natural sciencesbiological sciencesgeneticsgenomes
Parole chiave
Programma(i)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Argomento(i)
Invito a presentare proposte
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01
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HORIZON-EIC - HORIZON EIC GrantsCoordinatore
75006 Paris
Francia