Bioanalytics
Ryan Hill (he/him/his)
Senior Principal Scientist
Drug Disposition/ADME/Eli Lilly and Company
Indianapolis, Indiana
Enaksha Wickremsinhe, PhD (he/him/his)
Bioassay Development Lead
Bill and Melinda Gates Medical Research Institute
Cambridge, Massachusetts
Recent advancements in oligonucleotide delivery have led to a growing need to develop robust bioanalytical methods to quantify exposure and further characterize siRNA structural changes in biological fluids and tissues. This paradigm is unlike small molecule workflows where the need to characterize delivery not only to target tissue but cellular uptake to specific compartments is incorporated into bioanalytical assay development. Mass spectrometry has shown to be a powerful bioanalytical tool in ADME early-stage discovery due to the broad flexibility in sample preparation procedures to target specific aspects of molecular chemistry coupled to the selectivity at detection. In this presentation, we will discuss assay development considerations to support diverse biochemical natures of oligonucleotide therapeutics supporting various targeted immunoprecipitation techniques compared to low reagent specific considerations such as solid phase extraction coupled to high resolution mass spectrometry detection. Overall, we will discuss the challenges associated with oligonucleotide measurement in support of product development, advantages of specific techniques, and future perspectives in oligonucleotide assay development.