The Molecular Architecture of Cationic Lipid Nanoparticles for siRNA Delivery

The proposal aims to use SANS and contrast variation to determine the detailed molecular architecture of lipid nanoparticles (LNPs) containing the nucleic acid, siRNA. The information thus gained will aid an understanding of the relationship between the cationic lipids used to prepare the LNP, the structure of the LNP they form and the LNP's therapeutic activity. Recently, work in our group has shown that the preparation of LNPs using trichain cationic lipids results in better siRNA delivery than when using the more usual dichain cationic lipids. The current proposal will therefore use SANS to compare the molecular architecture of LNPs prepared using trichain cationic lipids with that seen with the corresponding dichain lipids and relate this to the ability of the LNPs to deliver siRNA. The work is important for the development of improved nucleic acid delivery vehicles as medicines.