Interaction of RNA with titratable bilayers

Lipid nanoparticles (LNPs) are a growing area of interest as drug delivery vehicles in mRNA therapies. Therapeutically relevant LNPs are complex, multicomponent systems with strongly pH dependent structure and interactions. Arteta et al. 2018 previously characterised an LNP system, which includes the cationic ionisable lipid DLin-MC3-DMA (MC3) and has shown therapeutic potential in vivo. The complex internal structure of these LNPs is poorly understood, therefore so is the interaction of MC3 with the mRNA cargo. To understand the complex system of Arteta et al, we propose to use a simpler system with the key components thought to control the RNA interaction. This consists of a two component lipid bilayer containing DOTAP (cationic lipid) or MC3 (titratable cationic lipid) and DOPC (phospholipid), which will allow us to reveal the effect of pH and charge density on adsorption of mRNA.