Effect of charge ratio and polycation structure on early stage kinetics of nucleic acid-based complex formation studied through stopped-flow

The study of polyelectrolyte complexes for applications in nucleic acid-based therapies is currently attracting great interest due to the emergence of mRNA vaccines. While many complexes have been examined in gene transfection assays, only few studies have investigated the ultrafast kinetics of nucleic acid complexation. Recently, we used the stopped-flow light scattering technique to study the early-stage complexation kinetics of a model system composed of calf-thymus DNA and chitosan. Time-Resolved Small-Angle X‐ray Scattering on ID02 is the best suited approach to study the complexation mechanism. Our goal is to determine the size and morphology of complexes formed at the early-stage kinetics and to explain the effect of charge ratio and polycation structure on complexation mechanism. This proposal represents the first stage of a more ambitious project that aims at elucidating the different steps of the disassembly of nucleic acid-based complexes in physiological conditions.