Stirring Things Up: Integrating Stirred-Bed SPOS and Enzymatic Ligation for Industrial Oligonucleotide Production

The rising demands for therapeutic oligonucleotides requires scalable, efficient, and more sustainable manufacturing solutions. Stirred bed technology (SBT) presents an exciting opportunity for the industry. In this presentation, we explore the unmet needs in oligonucleotide production, and how Bachem’s stirred bed approach overcomes the constraints of conventional flow-through SPOS technology. We also unpack three case studies which demonstrate successful production of therapeutic oligonucleotides, and highlight the benefits of combining stirred bed technology with enzymatic ligation for fragment-based synthesis and continuous purification methods.

Key takeaways

• Stirred bed technology (SBT) for solid‑phase oligonucleotide synthesis (SPOS) introduces a novel reactor and mixing concept that eliminates the flow‑related inhomogeneities of conventional packed‑bed systems.
• Continuous stirring ensures uniform reagent distribution, seamless scalability and demonstrates resin swelling tolerability.
• SBT SPOS is fully compatible with state of the art downstream and hybrid manufacturing concepts, including enzymatic ligation and advanced purification strategies such as MCSGP. This seamless integration of chemical synthesis and enzymatic steps creates a powerful manufacturing platform.
• Overall, SBT SPOS provides a highly efficient, scalable, and future-proof manufacturing platform, enabling sustainable industrial oligonucleotide production at industrial scales.

About the speaker

Marco Minuth
Director Oligo R&D

Marco Minuth is Director Oligo R&D II at Bachem, where he leads a team dedicated to advancing process development for therapeutic oligonucleotides and pioneering new manufacturing technologies. He earned his PhD in organic chemistry from the University of Stuttgart, focusing on the synthesis of C‑nucleosides for high‑fidelity base pairing in oligonucleotides. . Having joined Bachem in 2015 as a Project Chemist in the API division, he has since held several positions within Peptide R&D, before transitioning to Senior Group Leader CMC, ultimately progressing into his current role.