Production of mRNA lipid nanoparticles using advanced crossflow micromixing

Lipid nanoparticles (LNPs) play a crucial role in RNA-based therapies, and their production is generally based on nanoprecipitation and coalescence of lipids around an RNA core. This process is primarily controlled via the rate of ethanol-lipid to mRNA aqueous phase mixing. When considering a manufacturing process for LNPs, choosing between single-use and reusable systems influences production efficiency, cost, and sustainability. Single-use systems offer advantages in minimising contamination and downtime, while reusable systems reduce plastic use, avoid the problem of leachables, especially in solvents and present long-term cost savings. Our results demonstrate the reproducible production of mRNA-LNPs with controlled Critical Quality Attributes, including high mRNA encapsulation from the initial screening scale through to GMP-scale production, where the same mixing ratio can be adopted across all product speeds from 30 to 500 mL/min used. These mRNA-LNPs were confirmed to be effective as therapeutics (protein expression) and for vaccination (antibody and cytokine responses).