Objectif Genetic diseases can only be truly cured via restoration of defective gene function. Homologous recombination is the ultimate tool for gene replacement, but is limited by low efficiency and reproducibility. DNA double-strand breaks enhance the efficiency o f homologous recombination in vitro dramatically, however for in vivo applications absolute site-specificity is crucial.Engineered, highly specific DNA endonucleases (meganucleases) with programmable specificity are the key to a wider use of homologous recombination in gene replacement. MenuG seeks to develop meganucleases that cleave only at positions of interest in a genomic context with the aim to solve - based on homologous recombination - the main problem in gene therapy: to replace genes efficiently, selectively and reproducibly.Three types of meganucleases will be engineered:- programmed restriction enzymes,- novel or redesigned homing endonucleases,- redesigned Type IIS restriction enzymes.These will be tested for in vitro cleavage specificity, delivery into the nuclei, in vivo cleavage specificity and induction of double-strand break repair by homologous recombination. Promising meganucleases will be tested for gene replacement in Pompe metabolic disease.Concepts for commercial applications will be developed. MenuG is a high-risk project, starting from the engineering of programmable meganucleases to efficient cell delivery and specific action on a defined genetic locus. It has a high impact profile with potentially enormous benefits primarily in the treatment of inherited monogenetic diseases, but in principle also of multigenic disorders, including cancer. Its innovative and visionary concepts are in the spirit of ADVENTURE.MenuG is multidisciplinary (comprising biochemistry, molecular, structural and cell biology, medicine, biotechnology, nanotechnology); its truly ambitious goals can only be achieved at a European level by pooling expertise from academic and industrial units. Champ scientifique sciences médicales et de la santébiotechnologie médicalegénie génétiquethérapie géniquesciences naturellessciences biologiquesgénétiqueADNsciences naturellessciences biologiquesbiologie cellulairesciences médicales et de la santémédecine cliniqueoncologiesciences naturellessciences biologiquesbiochimiebiomoléculeprotéinesenzyme Mots‑clés Gene Replacement Pompe disease homing endonucleases homologous gene targeting meganucleases metabolic disorders restriction endonucleases type IIS restriction endonucleases Programme(s) FP6-POLICIES - Policy support: Specific activities covering wider field of research under the Focusing and Integrating Community Research programme 2002-2006. Thème(s) NEST-2003-1 - Adventure activities Appel à propositions FP6-2003-NEST-B-3 Voir d’autres projets de cet appel Régime de financement STREP - Specific Targeted Research Project Coordinateur FOUNDATION FOR RESEARCH AND TECHNOLOGY - INSTITUTE OF MOLECULAR BIOLOGY AND BIOTECHNOLOGY Adresse Vassilika vouton Heraklion Grèce Voir sur la carte Liens Site web Opens in new window Contribution de l’UE Aucune donnée Participants (5) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire CELLECTIS S.A. France Contribution de l’UE € 0,00 Adresse 102, route de noisy Romainville Voir sur la carte Liens Site web Opens in new window Autres sources de financement Aucune donnée DIREVO BIOTECH AG Allemagne Contribution de l’UE € 0,00 Adresse Nattermannallee 1 Cologne (köln) Voir sur la carte Liens Site web Opens in new window Autres sources de financement Aucune donnée INSTITUTE OF BIOTECHNOLOGY Lituanie Contribution de l’UE € 0,00 Adresse Graiciuno 8 Vilnius Voir sur la carte Liens Site web Opens in new window Autres sources de financement Aucune donnée JUSTUS-LIEBIG-UNIVERSITAT Allemagne Contribution de l’UE € 0,00 Adresse Ludwigstrasse 23 Giessen Voir sur la carte Liens Site web Opens in new window Autres sources de financement Aucune donnée UNIVERSITY MEDICAL CENRE GRONINGEN Pays-Bas Contribution de l’UE € 0,00 Adresse Hanzeplein 1 Groningen Voir sur la carte Liens Site web Opens in new window Autres sources de financement Aucune donnée
