Objective A foremost health problem stems from the burden of degenerative diseases, including heart failure, neurodegeneration, retinal degeneration and diabetes, essentially linked to the aging of the human population and the incapacity of post-mitotic tissues to undergo efficient repair. This is an ambitious, highly innovative project aimed at developing an in vivo selection procedure, based on gene transfer of two genetic libraries cloned into Adeno-Associated Virus (AAV)-based vectors, for the identification of novel secreted factors or microRNAs providing benefit against various degenerative diseases. Two arrayed libraries will be generated, one coding for ~1,300 cDNAs from the mouse secretome, the other for all known microRNAs (~800 genes). Pools of vectors from each library will be obtained with serotypes suitable for in vivo transduction of different organs. The vectors will be injected in a series of mouse models of degenerative disorders involving damage to cardiomyocytes,, neurodegeneration, retinal degeneration and loss of beta-cells in the pancreas. The degenerative conditions will drive the selection for secreted factors or miRNA putatively preventing cell apoptosis, enhancing residual cell function or, in the best possible scenario, promoting tissue regeneration. This in vivo selection approach, which is supported by very encouraging preliminary results, has never been attempted before and is rendered possible by the property of AAV vectors to be produced at high titers, infect tissues at high multiplicity, persist in the transduced cells for prolonged period of times and efficiently express their transgenes in vivo. In addition to its final goal of identifying novel biotherapeutics, the project entails the successful achievement of several intermediate objectives and is expected to extend both technology and knowledge beyond the state-of-the art. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesclinical medicineophthalmologymedical and health sciencesclinical medicinecardiology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2009-AdG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY Address Padriciano 99 34149 Trieste Italy See on map Region Nord-Est Friuli-Venezia Giulia Trieste Activity type Research Organisations Administrative Contact Decio Ripandelli (Mr.) Principal investigator Mauro Giacca (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 1 824 000,00 Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY Italy EU contribution € 1 824 000,00 Address Padriciano 99 34149 Trieste See on map Region Nord-Est Friuli-Venezia Giulia Trieste Activity type Research Organisations Administrative Contact Decio Ripandelli (Mr.) Principal investigator Mauro Giacca (Prof.) Links Contact the organisation Opens in new window Website Opens in new window
