Efficient Large-scale siRNA Manufacturing: Enzymatic Ligation of Short RNA Fragments

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.

About the Speaker

Arne Berthelmann

Senior Director Oligonucleotide R&D

Arne Berthelmann studied chemistry at the Humboldt University Berlin, Germany. He then joined the group of Prof. J. Eichler at the Friedrich-Alexander-University Erlangen, where he obtained his Ph.D. for designing and synthesizing peptide inhibitors and vaccines in 2014. In the same year he started his career as project chemist with Bachem in Switzerland. Arne took a position as team leader of the API CMC development group after a short while and later on as director of the CMC development unit, where he started to work on oligonucleotides focusing on innovative technologies. Since beginning of 2023 he is leading Bachem’s oligonucleotide R&D team as Sr. Director focusing on process development and research with still a special interest in innovative technologies.

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