Dissociation mechanisms of complexes containing nucleic acids for gene release – DIMECO

Natural or synthetic polycations and lipids, are used in nucleic acid therapeutics, such as the mRNA vaccine field and gene therapy, as vectors that interact electrostatically with nucleic acids, condense them into nanoparticles, protect them and control their entry and release into cells. While the literature on the formation of complex particles is very well documented, much less studies have focused on the physical chemistry behind the endosomal escape disassembly, in particular in physicochemical conditions found in endosomal compartments and in an intracellular environment. This project aims to study the dissociation mechanisms of complexes containing nucleic acids (DNA, siRNA, mRNA) and either natural/synthetic polycations or cationic lipids in conditions found in extra- and intracellular medium: in presence of biological polyanions, osmolytes and lipid membranes. This knowledge will provide the basis for future improvement of the efficacy of nonviral vectors for gene deliver