Projektbeschreibung
Ein fortschrittlicher Ansatz zur Geneditierung
In den vergangenen Jahren hat es im Bereich der Genomeditierungstechnologien auf der Basis des CRISPR/Cas-Systems einige Fortschritte gegeben. Dieses System, eine angepasste Form eines bakteriellen Mechanismus zur Immunabwehr, nutzt RNS-Moleküle zur Bindung der Zielsequenz und des Cas-Enzyms, um die DNS an der gewünschten Stelle zu spalten. Für die Abgabe dieser Komponenten in die Zellen kommen gegenwärtig virale Vektoren zum Einsatz, die jedoch ein beträchtliches Toxizitätsrisiko darstellen. Das vom Europäischen Innovationsrat finanzierte Projekt EdiGenT stellt ein nichtvirales System auf Nanopartikel-Basis vor, das die Nebenwirkungen bei der Abgabe von Komponenten zur Geneditierung auf ein Minimum reduziert. In Kombination mit fortschrittlichen Prime-Editing-Molekülen gewährleistet es eine Genommodifizierung ohne die verheerenden Folgen von DNS-Doppelstrangbrüchen.
Ziel
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.
Wissenschaftliches Gebiet
- 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
Schlüsselbegriffe
Programm/Programme
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
HORIZON-EIC - HORIZON EIC GrantsKoordinator
75006 Paris
Frankreich