Program

Poster Presentations

Day 2, June 11（Thu.）　　Room P (5F 501+502)

2P-48

PDF

Uncovering Manufacturing Driven Variability in Phosphorothioate Oligonucleotide Isomer Profiles with cyclic Ion mobility MS

(¹Waters, ²Nihon Waters)
Jonathan Fox¹, ^oTaiji Kawase², Laetitia Denbigh¹

Synthetic oligonucleotides are promising therapeutics that modulate gene expression to treat and prevent disease. Their stability and pharmacokinetic properties are frequently enhanced through the introduction of phosphorothioate (PS) linkages, each of which creates an Sp or Rp chiral center. Across a full-length sequence, this results in a 2ⁿ diastereomeric space, generating thousands of possible isomers that may influence both pharmacodynamic and pharmacokinetic behavior, while making comprehensive structural characterization extremely challenging.
In addition to sequence‑dependent variability, differences in manufacturing processes can alter PS isomer distributions and potentially impact biological performance. To investigate this effect, we compared the same PS‑modified oligonucleotide sourced from multiple suppliers. Using the SELECT SERIES™ Cyclic™ IMS platform, we resolved and contrasted supplier‑dependent diastereomeric profiles, enabling detailed assessment of stereochemical consistency across manufacturing origins.

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