Light scattering solutions for multi-attribute quantification of mRNA-lipid nanoparticle therapeutics

Light scattering techniques deliver multi-attribute quantification (MAQ) of mRNA and lipid nanoparticle-formulated mRNA and can play a key role in product and process development as well as quality control of mRNA-LNP therapeutics. Specifically, multi-angle light scattering (MALS) coupled to separation by field-flow fractionation (FFF) or size-exclusion chromatography (SEC) provides high-resolution quantification of several mRNA and LNP attributes including size distribution, physical stability, LNP number concentration, morphology, and mRNA and lipid concentration.

The method can also be applied to evaluate how these attributes are affected by preparation, formulation, and storage conditions. In addition to high-resolution MAQ by SEC/FFF-MALS, dynamic light scattering (DLS) and electrophoretic light scattering (ELS) can be used for rapid, automatable batch measurements of particle size and concentration, polydispersity, and zeta potential, enabling rapid screening of the impact of different ions, ionic strength, pH, temperature and other parameters on the biophysical properties and stability of mRNA and LNP-mRNA.

Learning Objectives:

• How to bring multi-attribute quantification to LNP and mRNA characterization

• Considerations for technology selection for LNP and mRNA

• What rapid screening light scattering techniques exists today for LNP and mRNA formulation optimization

Presenter: Martin Kurnik, Ph.D. (Application Scientist, Analytical Sciences, Waters/Wyatt Technology)

Martin Kurnik joined the Analytical Sciences team at Waters | Wyatt Technology in 2021, where he helps customers identify and develop the best solutions for their analytical needs. As an application scientist, Martin leverages his expertise in multi-angle light scattering and dynamic light scattering as well as a wide range of other leading techniques for biomolecular characterization. His postdoctoral research in protein folding and misfolding biophysics focused on understanding and preventing misfolding in bulk solution and on artificial surfaces used in medicine and biotechnology, and he has also developed protein- and aptamer-based electrochemical biosensors for continuous real-time measurements in vitro and in vivo. Martin received his M.Sc. in Chemistry and Ph.D. in Biochemistry from Stockholm University, Sweden.