Breakthrough in Liquid Phase Oligonucleotide Synthesis: Nanostar Sieving® Enables First Large-Scale, Fully Liquid Process
Exactmer is delighted to share that our latest article, “Fully liquid phase oligonucleotide synthesis” has been published in Organic Process Research & Development. The paper showcases pivotal early advances in the Nanostar Sieving® platform and sets a new benchmark for liquid-phase oligonucleotide synthesis (LPOS).
In a milestone achievement for LPOS, Exactmer describes the production of a 21-mer siRNA and a 16-mer ASO-like gapmer, synthesized exclusively in the liquid phase. Both PO and PS backbones have been produced as well as deoxy sequences, all while maintaining the oligo in a single-solvent solution from initial coupling through to isolation. This establishes the route to large-scale oligo manufacturing, using Exactmer’s proprietary membranes as spiral wound modules (SWMs), enabling organic solvent nanofiltration at industry-relevant scales.
The paper is co-authored by partners from AstraZeneca, Alnylam, Novartis and CPI, through the Grand Challenge 3 (GC3) collaboration. Together, this consortium laid the foundation for advancing Exactmer’s Nanostar Sieving® platform for therapeutic oligo manufacture at large-batch production volumes. Nanostar Sieving® is Exactmer’s proprietary platform technology which uses membrane-assisted liquid-phase synthesis to produce sequence-defined polymer therapeutics. The platform continues to gain strong momentum in the oligo synthesis market for its capacity to supply large-volume batches, critical for the supply of oligo medicines to patients suffering from prevalent diseases such as cardiovascular disease and Alzheimer’s.
“This work showcases Exactmer’s early innovation in the Nanostar Sieving technology, which have importantly underpinned the oligo manufacturing strategies we have in place today.” Said Prof. Andrew Livingston, senior author and CEO of Exactmer. “Led by an industrial research collaboration, we have broken the record for the longest oligo yet to have been synthesised entirely in the liquid phase.”
The full paper has been published on 12 December 2025 in Organic Process Research & Development.
Contact
Dr Cristina Bertulli, VP of Business Development – [email protected]
