Developing Lipid Nanoparticles for the delivery of mRNA.

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The efficacy of messenger ribonucleic acid (mRNA) vaccines is now well demonstrated, leading to the use of mRNA-based COVID-19 vaccines delivered using lipid nanoparticles. Lipid nanoparticles (LNPs) are a key component of these vaccines as they protect the mRNA from degradation in the body and mediate delivery into the cytoplasm of cells. Generally, LNPs are comprised of various ratios of a neutral structural lipid, cholesterol, a PEG-lipid (to control particle size), and an ionisable lipid (which is cationic at low pH and thus binds the mRNA, and near-neutral charge at physiological pH). However, there is a wide range of choices to consider when designing an optimal mRNA-LNP formulation, and the impact of the lipid choice selected is not well understood. Therefore, the aim of this project is to support the implementation of screening and characterisation of LNPs for mRNA delivery in conjunction with the IntraCellular Drug Delivery Centre of Excellence (ICDDC) and CPI. This will involve: 1) high-throughput preparation of LNPs, 2) high-throughput analytical characterisation of LNPs and 3) rapid potency screening tools. This deliverable of this programme will be the implementation of this screening to optimise LNPs which identifies lead formulations, provides significant savings in time and resources and de-risks early-stage LNP formulation development.