Linear synthesis by continuous-flow SPOS is the current state-of-the-art technology to manufacture oligonucleotide APIs. A very promising alternative, especially to manufacture large quantities, is the enzymatic ligation of short oligonucleotide fragments. This approach offers several advantages compared to the conventional strategy like higher yields and reduced purification burdens.Bachem and Codexis will present a case study focusing on a therapeutically relevant siRNA sequence and benchmark different technologies used to manufacture siRNA fragments. We will discuss a wholistic view of the manufacturing process and review control strategies for residual enzyme.
Knowledge Center
Webinar Efficient Large-scale SiRNA Manufacturing: Enzymatic Ligation of Short RNA Fragments
05 November 2025
Webinar Efficient Large-scale SiRNA Manufacturing: Enzymatic Ligation of Short RNA Fragments
About the Speakers
Benjamin Breitenbach earned his Ph.D. in Polymer guided drug delivery from Johannes Gutenberg University Mainz in 2019. He then joined Ascendis Pharma as a Bench Scientist, focusing on biopolymer hydrogel chemistry. In 2021, Benjamin joined Bachem as a group leader in Oligo Production I, later in Oligo R&D I and since October 2024, he is serving as Senior Group Leader in Oligo R&D I, driving innovation in oligonucleotide development and production.
Mathew Miller joined Codexis in 2009, and has worked on enzyme engineering projects including T7 RNA polymerases for mRNA manufacturing, enzymatic oligo synthesis, and RNA ligation technologies. He is currently focused on enzymatic routes for siRNA synthesis. Dr. Miller received his Ph.D. from the University of California, San Francisco.
