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Development of Polymeric Nanovehicles for siRNA Delivery in Cardiomyocytes

Cardiovascular diseases are the first cause of death worldwide. In these diseases, Ca2+ handling plays an essential role. Mitochondria, the main sources of energy in eukaryotic cells, are important Ca2+ regulators. However, under pathological conditions, mitochondrial energy production may be altered due to mitochondrial Ca2+ overload. Therefore, there is an increasing interest in developing cardiovascular therapies with mitochondrial molecular targets. Among these therapies, gene therapy has great importance due to its overwhelming effects. However, an effective in vivo cardiovascular gene transfection vehicle has not been developed. This project consists in the design and development of a biodegradable and biocompatible nanovehicle suitable for siRNA delivery to in vivo systems, with the objective of decreasing mitochondrial dysfunction in myocardial cells through the reduced expression of the Mitochondrial Calcium Uniporter (MCU), protein which transports Ca2+ from the cytosol into the mitochondria.