Structural characterization of lipoplexes for nucleic acid delivery.

Since the COVID-19 pandemic and the success of the mRNA vaccines, RNA encapsulated in lipid nanoparticles have emerged as an efficient delivery system for nucleic acid-based therapeutics. Recently we have developed new formulations of lipoplexes (i.e. complex multilamellar vesicles) which are a promising tool for NA-based therapeutic delivery systems. This proposal aims to study the internal structural organization of the lipoplexes by varying several parameters: : type of nucleic acid used (pDNA, mRNA, siRNA, ASO), process parameters, lipid composition (especially the influence of ionizable lipids), and environmental parameters (temperature and pH). Synchrotron-SAXS will allow us to accurately characterize the multilamellar organization of the lipoplexes, which is challenging with other methods. The results will provide insight into the complex structure of lipoplexes and contribute to the development of improved delivery systems for mRNA and other NA therapeutics.