Rapid and flexible analytical characterization of oligonucleotides

About this webinar

Therapeutic oligonucleotides (ASOs, siRNA and conjugates) present analytical challenges due to their structural diversity and chemical modifications. In early discovery, robust UV×MS purity assessment and impurity profiling are essential for both crude oligonucleotide libraries prior to early screening and purified batches prior to advanced assays.

Here, we present a streamlined LC–UV–MS platform comprising two methods paired with (semi-)automated data processing to increase analytical throughput and accelerate decision-making. First, a flexible characterization method provides chromatographic separation and UV×MS purity/impurity analysis for purified ASOs, siRNA and conjugates, with semi-automated processing and automated reporting enabled by the Byos Oligo App. Second, a high-throughput method delivers online desalting, rapid MS fingerprinting, purity analysis and impurity-class profiling for crude ASO and siRNA single‑strand libraries at scale (hundreds per day).

Together, these methods provide a fast, scalable and fit‑for‑purpose framework for oligonucleotide characterization in early drug discovery.

Key takeaways:

• Fit‑for‑purpose LC–UV–MS workflows We developed two analytical methods, one for detailed characterization of purified batches and one for high‑throughput screening of crude libraries, covering early discovery needs.
• (Semi-)automated data analysis We integrated data analysis tools, such as the Byos Oligo workflow, to enable semi‑automated UV×MS purity determination and impurity assignment with automated reporting, reducing manual effort and variability.
• Standardized reporting We implemented standardized outputs to deliver consistent purity/impurity metrics for oligonucleotides, improving comparability across libraries and individual samples.

Our Speakers

Dr. Kathrin Stavenhagen is an Associate Principal Scientist in Discovery Sciences at AstraZeneca, Sweden, with extensive experience in LC-MS-based characterization of oligonucleotides and complex biomolecules. She played a vital role in building LC-MS platforms for oligonucleotide analytical characterization to support chemistry teams and earned her PhD from VU University Amsterdam.

Dr. Manasses Jora supports medicinal chemistry at AstraZeneca, Sweden, focusing on early oligonucleotide drug discovery—primarily siRNAs and ASOs. He earned his B.S. and M.S. in Chemistry from Brazil and has authored multiple peer-reviewed publications on the characterization of natural and therapeutic nucleic acids using LC-MS techniques.