Objective 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. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencescell biologymedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords 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. Topic(s) NEST-2003-1 - Adventure activities Call for proposal FP6-2003-NEST-B-3 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator FOUNDATION FOR RESEARCH AND TECHNOLOGY - INSTITUTE OF MOLECULAR BIOLOGY AND BIOTECHNOLOGY Address Vassilika vouton Heraklion Greece See on map Links Website Opens in new window EU contribution € 0,00 Participants (5) Sort alphabetically Sort by EU Contribution Expand all Collapse all CELLECTIS S.A. France EU contribution € 0,00 Address 102, route de noisy Romainville See on map Links Website Opens in new window DIREVO BIOTECH AG Germany EU contribution € 0,00 Address Nattermannallee 1 Cologne (köln) See on map Links Website Opens in new window INSTITUTE OF BIOTECHNOLOGY Lithuania EU contribution € 0,00 Address Graiciuno 8 Vilnius See on map Links Website Opens in new window JUSTUS-LIEBIG-UNIVERSITAT Germany EU contribution € 0,00 Address Ludwigstrasse 23 Giessen See on map Links Website Opens in new window UNIVERSITY MEDICAL CENRE GRONINGEN Netherlands EU contribution € 0,00 Address Hanzeplein 1 Groningen See on map Links Website Opens in new window
