SANS study of pH-induced structural alteration of lipid nanoparticles for gene delivery

We have studied lipid nanoparticles (LNPs) prepared from an ionisable cationic lipid, a helper lipid, a cholesterol and a poly(ethylene glycol) (PEG) lipid via a microfluidic system. This 4-component system mimics the LNP nanocarriers used in the delivery of COVID-19 vaccines by Pfizer and Moderna. Our recent studies have revealed vast variations in the transfection and expression efficiency of LNPs in both in vitro and in vivo experiments from substituting some ingredients with their analogs. Furthermore, pH environment also has a huge impact on their nanostructures. As LNPs are internalized via emdosomal cycling during which pH gradually becomes acidic, we request 3 days of SANS2D to undertake the proposed work and cover the widest Q range for better structural resolution,