New Insights on Anion Exchange and Size Exclusion of Nucleic Acids

The recent success of mRNA vaccines demonstrates the capabilities of nucleic acid-based drugs. These new modalities hold the promise of delivering not only potent vaccines, but also enzyme replacement therapies. However, there is a need for more analytical characterization tools to provide more informationon stability, heterogeneity, drug design and structure-function relationships. Anion-exchange (AEX) and size exclusion (SEC) chromatography techniques are well suited to providing high resolution separations of nucleic acids and their carriers.

AEX and SEC offer comprehensive quality and impurity profiling, but have suffered with previous methods from unsatisfactory recovery and resolution, poor MS compatibility. In addition, column hardware and packing materials have exhibited problematic secondary interactions. We have explored alternative mobile phase conditions in combination with various packing materials and sorbents in parallel with using novel low adsorption hardware allowing for more robust platform method for multiple drug substances and sample types, including AAVs and mRNA.

Learning Objectives Include:

• Comprehensive overview of both theoretical and practical aspects of modern AEX and SEC separations.

• New solutions and method parameter consideration for design of robust methods for nucleic acid separations.

• Chromatography examples for small to very large nucleic acids

Presenter: Szabolcs Fekete PhD (R&D Investigator, Waters Corporation)

Dr. Szabolcs Fekete worked as an analytical R&D scientist in the pharmaceutical industry for 10 years then moved to the University of Geneva and worked as a scientific collaborator for a decade. In April 2021, he joined Waters Corporation and now works as one of the Chemistry department’s lead application and development scientists. . He has contributed to 200 pieces of published work.