Following the initial formation of Lipid NanoParticles by solvent quenching

LNPs are fabricated via rapid-mixing at low pH, where lipids dissolved in alcohol are combined with the acidic aqueous phase containing the mRNA (volume ratio 1:3 ethanol:water), leading to high entrapment efficiencies. Subsequent processing involves dialysis to remove ethanol and neutralize the pH, creating LNPs of neutral surface charge. Understanding the mechanisms behind mRNA-LNP formation is crucial for improving their design. We wish to investigate the fast formation of LNPs by rapid mixing of the molecular alcoholic solution of lipids and the aqueous phase, with a stopped-flow device. We will compare results obtained without RNA, and with RNA of different lengths to cover the entire relevant range.