Director - Analytical Chemistry Eli Lilly and Company, Indiana
Antibody-RNA conjugates (ARCs) represent an emerging class of biotherapeutic molecules that combine the tissue-targeting specificity of monoclonal antibodies with the gene-silencing activity of small interfering RNA. The unique structural characteristics of ARCs can impact how they perform in traditional analytical methods commonly used for characterization. Under conventional SEC conditions, we observed high variability across multiple SEC column chemistries, preventing reliable quantitation of size variants. The source of the observed SEC variability for ARC molecules is discussed and A novel ion-pairing SEC mobile phase conditions which resolves the variability issue and greatly improved the robustness of the SEC method is presented.
Learning Objectives:
Appreciate the complexities of analytical method development for new modalities including antibody RNA conjugates
Understand and troubleshoot size exclusion chromatography methods
Think outside the box to solve an issue with a common technique
