Insights into the lipid inverse liquid crystalline mesophase behaviour of ionisable lipid nanoparticles encapsulating mRNAs by time-resolved

Gene therapeutics using mRNAs, DNAs, and siRNAs hold great potential to revolutionise many disease prevention and treatment. The quest for safer, more effective, cell-specific, and organ-targeting delivery system for the nucleic acids still needs significant research effort. This proposal aims to use the ESRF ID02 beamline, in particular its time-resolved, rapid-mixing stopped-flow apparatus, to investigate the lipid nanoparticles (LNPs) as gene delivery systems. In particular, various novel LNP formulations and the benchmark clinical LNP formulation replicates (used in the COVID-19 mRNA vaccines) will be systematically studied at the ID02 beamline in terms of their self-assembly process and structure formation kinetics upon mixing with mRNAs in aqueous solutions or mixing with proteins in serum. The improved understanding of the structure-function relationship will have a significant impact in designing safer and more effective LNPs with cell and organ targeting ability.