During the COVID-19 pandemic, mRNA vaccines, which use lipid nanoparticles (LNPs) to deliver their instructions to cells, saved millions of lives. These LNPs are made up of several components: ionizable lipids, helper lipids, cholesterol, and polyethylene glycol-conjugated lipids. However, current mRNA vaccines can cause strong immune reactions because of the ionizable lipids. Additionally, some LNPs in the vaccine formulations are empty, which can trigger immune responses and reduce the effectiveness of mRNA treatments.

The aim of this HALRIC pilot project is to improve mRNA-LNP design and formulation for therapeutic application, by understanding how the structure and function of the different particle types are related in a single formulation.

The research team believes that reducing the number of empty LNPs could help develop better mRNA treatments by lowering unwanted immune reactions and increasing the amount of protein produced by the mRNA. To test this idea, they will study the different populations of particles in the current LNP formulations.

They will use a method called Asymmetric Flow Field-Flow Fractionation combined with Small Angle X-ray Scattering to look at the structure of each type of particle. At the same time, they will measure how much mRNA each type contains and how much protein it produces. By linking these structural and biological findings, they hope to understand how the structure of the particles affects their function. This knowledge will help them design better LNPs for delivering mRNA more effectively in therapeutic applications.

For further information about this HALRIC pilot project, please contact:
Federica.Sebastiani@sund.ku.dk
University of Copenhagen