Comparison of MALS-Based Analyses of Large mRNA

This application note presents a comparison of size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) for analyzing large mRNA samples using two different widepore columns. The columns evaluated are the GTxResolve Premier SEC 1000 Å 3 µm Column and a similar manufacturer A 1000 Å 2.7 µm column. The objective is to assess their performance in terms of resolving dimeric species and providing reliable mass and size characterization of mRNA. The GTxResolve column demonstrated superior performance with lower light scattering noise, allowing for accurate analysis even with minimal sample amounts. The document details the experimental setup, including sample preparation, column conditioning, and measurement protocols. It emphasizes the importance of achieving minimal noise levels for effective MALS measurements and discusses the implications of column design on analytical outcomes. The findings suggest that the GTxResolve column is more suitable for high-throughput screening of mRNA therapeutics, particularly in scenarios with limited sample availability.