The influence of cholesterol on the ability of ionisable cationic lipid to interact with nucleic acid in lipid nanoparticles

Lipid nanoparticles (LNPs) are increasingly being used to deliver nucleic acids and have reached world-wide prominence as the delivery vehicle for the COVID-19 vaccines produced by Moderna and Pfizer/Biontech. Yet few, if any, studies have examined the driving force for LNP self-assembly and, in particular, the structures formed as a result of the interaction of their nucleic acid cargo with the ionisable cationic lipid, MC3, and cholesterol, the components believed to comprise the interior of the LNPs. Preliminary surface pressure-area isotherms have shown strong effects of MC3 monolayers without/with cholesterol with nucleic acid in the subphase. The present study will exploit neutron reflectivity measurements on FIGARO to understand the effect of the helper lipid cholesterol on the ability of the MC3 lipid to interact with nucleic acid polyA.