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Contenido archivado el 2024-06-18

Generation of AAV-based, arrayed genetic libraries for in vivo functional selection: an innovative approach to identify secreted factors and microRNAs against degenerative disorders

Final Report Summary - FUNSEL (Generation of AAV-based, arrayed genetic libraries for in vivo functional selection: an innovative approach to identify secreted factors and microRNAs against degenerative disorders)

A foremost health problem stems from the burden of degenerative diseases, including heart failure after myocardial infarction. This is essentially due to the incapacity of several of our organs to undergo efficient repair in the adult life and during aging. Since organ repair and tissue regeneration are under the control of specific biological programs, there is much hope that specific biological molecules might be identified, such as proteins or nucleic acids, that might be used as true medicines to combat these conditions.
FunSel was a highly innovative project to discover novel biotherapeutic molecules against myocardial infarction and heart failure. It was based on the development of two large collections of viral vectors, one corresponding to the whole set of proteins secreted by the cells and the other to the short regulatory RNAs (microRNAs) encoded by the genome, and on a new procedure to screen these collections towards the identification of factors proving therapeutic benefit.
Application of this procedure has led to the discovery of at least 20 novel cytokines and growth factors and an approximately equal number of microRNAs that, through different mechanisms, protect myocardial cells against ischemia or promote cardiac regeneration.
Besides shedding light on some of the basic mechanisms that govern cardiac tissue formation and renewal during adult life, the discovered molecules hold great promise for development into effective therapeutics.