Time-resolved lipid-mRNA millisecond self-assembly kinetics toward assessment of clinically relevant formulations involving ionizable lipid

The aim of the proposal is to investigate the self-assembly process and lyotropic liquid crystalline nanostructural formation of ionizable lipid nanoparticles (LNPs) upon mRNA complexation, on a millisecond time scale using the rapid mixing stopped-flow device combined with the time-resolved SAXS capabilities of the high brilliance ID02 beamline. Driven by the successful clinical use and the exceptional potential of LNPs for mRNA delivery, this proposal will investigate the millisecond kinetics and structural formation of mRNA binding with a range of clinically relevant ionizable LNPs, including the BioNTech/Pfizer COVID-19 Vaccine LNPs (ALC-0315 and ALC-0159), and the Moderna COVID-19 Vaccine LNPs (SM-102 and PEG-DMG).