Abstract
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.In this work, the results of the first stage of this project will be presented. Two potential nanovehicles for siRNA delivery were designed, optimized and characterized with respect to size, surface charge and siRNA loading. The optimal size for both nanovehicles was ~100 nm, with surface charge close to neutrality through PEGylation, and a preliminary siRNA loading of 60 %. In addition, the nanovehicles have no cytotoxic effects up to 1000 μg/mL. Besides, the release profile and protection of siRNA is comparable to reported values using polymeric vehicles. These results show the possibility of developing an adequate siRNA delivery system with the potential of in vivo delivery to treat cardiovascular diseases through gene therapy.Support or Funding InformationALA is supported by CONACyT MSc scholarshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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