Combining neutron reflectometry and simulations to characterise interaction of model mRNA with cationic membranes

Cationic (or ionisable) lipids, along with neutral helper lipids and cholesterol, form a crucial component of lipid nanoparticles (LNPs), which are currently used as delivery agents for mRNA-based drugs (e.g Covid-19 vaccines). Despite the success in this area, there remain many challenges. The current formulation of these LNPs is highly unstable, therefore must be stored at very low temperatures. One of the main reasons for this instability is the degradation of mRNA inside the complex LNP environment. An understanding of interactions between RNA and cationic/neutral membranes would provide insight into the mechanism of this degradation and the stability and function of LNPs, therefore aid in the rational design of new formulations. The power of computational simulations to aid in analysis of experimental data from complex samples has grown and can be used to infer structural details.