Polymeric Nanoparticles for Gene Therapy: Development of vectors for delivery of messenger RNA and interfering RNA

Abstract

The Sars-Cov2 pandemic highlighted the great potential of therapeutic strategies involving gene therapy, mainly due to the development of vectors capable of delivering mRNA and siRNA molecules. Among the various polymers used in non-viral gene therapy, biodegradable low molar mass amphipathic polymers have shown great potential and generated several patents focusing on the release of mRNA and siRNA. In this area, we have been successful with the release of siRNA and, in a recent project, we have produced a provisory patent that is being developed by a Startup. This project proposes the development of vectors based on amphipathic oligomers. The construction of unpublished vectors of this proposal shares strategies used by lipid nanoparticles in the Sars-Cov2 vaccines, such as ionizable amino groups with variable pKas, an amphipathic nature, labile bonds that allow the disassembly of the system by intracellular stimuli and a hydrophilic coating to reduce premature elimination of NPs from circulation. The proposed structures aim to obtain bioresponsive nanovectors for the transport and release of siRNAs with a therapeutic focus on inflammatory diseases and the release of messenger RNAs focusing their application on vaccines. The methodology that will be applied in the synthesis and characterization of polymers, as well as the in vitro studies of nanoparticles, is based on the literature and recent work by our research group and will allow the selection of vectors with potential for in vivo studies. This project will also make the in vivo study viable within the ongoing project grant number nº 2019/27801-0. (AU)