REDWOOD CITY, Calif. — September 28, 2026
Codexis, Inc. announced an agreement with a pioneering siRNA drug innovator to use its ECO Synthesis® Manufacturing Platform to explore the production of stereo-defined oligonucleotide fragments. Under the collaboration, Codexis will apply its fully enzymatic manufacturing process to produce fragments with controlled phosphorothioate stereochemistry, which the partner will then assemble into final siRNA duplexes through ligation. The agreement builds on capabilities Codexis presented at TIDES USA 2026, where the company demonstrated full-length siRNA synthesis with precise stereochemical control through its StereoSelectSM technology. Financial and customer-specific details were not disclosed. The collaboration will evaluate whether enzymatic fragment synthesis can provide advantages in scalability, efficiency, purity and product quality compared with conventional solid-phase oligonucleotide synthesis.
ECO Synthesis Enables Stereo-Defined siRNA Fragments
Codexis will use its ECO Synthesis platform to manufacture stereo-defined oligonucleotide fragments through an aqueous enzymatic process. The approach is designed to provide control over the stereochemistry of phosphorothioate linkages, a feature that can be important in the manufacture and characterization of chemically modified oligonucleotides. Rather than producing the complete siRNA molecule through a conventional single manufacturing route, the collaboration will use enzymatically produced fragments that are subsequently assembled into the final duplex through ligation. Codexis said this fragment-based strategy is gaining interest as a potential next-generation manufacturing model for oligonucleotide therapeutics because it could support scalability, process efficiency and product-quality control. The current collaboration is focused on technology evaluation, and its results will help determine the potential application of the process in future clinical development programs.
Collaboration Compares Enzymatic and Solid-Phase Manufacturing
The companies will compare enzymatically synthesized oligonucleotide fragments with materials produced through conventional solid-phase oligonucleotide synthesis (SPOS). The evaluation will examine purity, product quality and ligation performance to determine how the ECO Synthesis approach performs against established manufacturing methods. The resulting data are intended to help the siRNA innovator assess whether enzymatic fragment production could be incorporated into future development and manufacturing workflows. Codexis previously demonstrated full-length siRNA synthesis with controlled phosphorothioate stereochemistry using its StereoSelect capability, providing the technical foundation for the current collaboration. Because the agreement is an exploratory technology collaboration, the comparison will be important in determining whether the observed manufacturing characteristics translate into practical advantages for therapeutic-scale production.
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Codexis Advances Next-Generation Oligonucleotide Manufacturing
The agreement expands Codexis’ efforts to industrialize enzymatic manufacturing for complex oligonucleotide therapeutics, particularly in the rapidly growing RNA interference (RNAi) field. The ECO Synthesis Manufacturing Platform uses aqueous enzymatic chemistry and is being developed as a potential scalable alternative to traditional solid-phase organic synthesis. Codexis says its approach is designed to potentially improve yield, purity, energy efficiency, waste generation and stereoisomer control, while supporting manufacturing capacity with potentially lower capital requirements. The company is initially applying the platform to RNAi therapeutics while continuing to supply high-performance enzymes through its BioCatalysis business for small-molecule pharmaceutical manufacturing. The new collaboration provides an opportunity to test ECO Synthesis with an established siRNA innovator and generate additional data on stereo-defined manufacturing as the industry evaluates alternative production technologies for next-generation oligonucleotide medicines.
Source Codexis, press release
