Codexis, Inc. announced it has successfully synthesized an oligonucleotide via an enzymatic route to support RNA-based therapeutics manufacturing. Data highlighting this historic manufacturing milestone are being presented on May 14, 2024 in a Spotlight Presentation at the TIDES USA annual meeting taking place in Boston, MA, and virtually May 14 ? 17, 2024.

Codexis Enzymatically Synthesizes Fully Modified RNA Oligonucleotide: During the presentation, Codexis will showcase data on the enzymatic synthesis of a known siRNA oligonucleotide that incorporates the nucleotide modifications most frequently found in approved therapeutic assets today. This includes the synthesis of siRNA compounds using the Company?s Enzyme Catalyzed Oligonucleotide (ECO) Synthesis manufacturing platform from a starter oligonucleotide to the inclusion of a conjugation moiety. This final step primes the oligonucleotide for the attachment of a customer?s proprietary targeting moiety to enable direct delivery of the therapeutic agent to the desired cells.

Key data from the presentation noted that the ECO Synthesis manufacturing platform: Incorporated RNA bases with common modifications used in current siRNA therapeutic assets; Achieved coupling efficiency greater than 98%; Executed the enzymatic addition of a conjugation moiety; and Confirmed lack of notable impurities typically observed in phosphoramidite chemistry synthesis. Now that Codexis has successfully achieved this important technical milestone, the Company is continuing process development to optimize yield, purity and quality with the goal of providing customers with siRNA material of comparable or better quality to phosphoramidite chemistry for preclinical testing. Codexis Launches RNA Ligase Screening and Optimization Services: Codexis also on May 14, 2024 announced the launch of its RNA Ligase Screening and Optimization Services.

An overview of this new offering will be highlighted during a TIDES Talk session on Thursday, May 16, 2024. During phosphoramidite chemical synthesis of RNA, each nucleotide added to the growing oligonucleotide amplifies inherent coupling errors, leading to a decrease in the yield of the desired full-length RNA construct. By utilizing a ligation approach, multiple short, single-stranded RNA (ssRNA) fragments can be synthesized, via phosphoramidite chemistry or the ECO Synthesis manufacturing platform, then duplexed and ligated together with an ecoRNA double-stranded ligase to form the desired double-stranded RNA (dsRNA) construct.

This method provides the potential for higher purity and yield, which allows for increased scalability and reduced manufacturing costs. As part of Codexis? Center of Excellence for Enzymatic RNA Synthesis, the Company provides RNA ligase screening and optimization services, which include the custom evolution of dsRNA ligase enzyme variants, screening and protocol optimization for manufacturing and use of the dsRNA ligase, and research-grade RNA production, which can be used for future preclinical studies.