Description du projet
Une approche avancée de l’édition de gènes
Ces dernières années ont été marquées par des avancées dans les technologies d’édition du génome basées sur le système CRISPR/Cas. Inspiré des mécanismes de défense immunitaire des bactéries, le système utilise des molécules d’ARN qui se lient à la séquence cible et l’enzyme Cas pour cliver l’ADN à l’endroit souhaité. Actuellement, l’introduction de ces composants dans les cellules se fait par l’intermédiaire de vecteurs viraux qui présentent toutefois un risque élevé de toxicité. Financé par le Conseil européen de l’innovation, le projet EdiGenT propose un système non viral à base de nanoparticules aux effets secondaires minimes pour la délivrance des composants d’édition de gènes dans les cellules. Associé à des molécules d’édition avancées, il garantit la modification du génome sans les conséquences néfastes des cassures de l’ADN double brin.
Objectif
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.
Champ scientifique
- 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
Programme(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Thème(s)
Régime de financement
HORIZON-EIC - HORIZON EIC GrantsCoordinateur
75006 Paris
France