Wednesday, September 23Wednesday, 23 September 2026 - EST (Eastern Time, UTC-05:00

Investigational seasonal influenza mRNA vaccines can elicit variable immune responses across influenza A and B antigens, with recent clinical trials of mRNA-based influenza vaccines showing relatively superior immune responses to influenza A strains compared to influenza B strains. We investigated whether antigen-intrinsic differences contribute to this variability in our mRNA vaccine candidates. We assessed the translational efficiency of influenza hemagglutinin (HA)-encoding mRNAs, intracellular trafficking of HA proteins, and the immunogenicity of multivalent mRNA vaccine candidates, including a novel antigen design, in mice. Our findings provide a mechanistic explanation for the lower expression and possibly immune response of influenza B antigens and suggest that antigen stabilization can improve their performance in mRNA vaccines.

RNAi innovators and manufacturers are increasingly adopting ligation-based approaches for siRNA production, driven by clear advantages in efficiency, scalability, and process simplicity relative to traditional solid-phase oligonucleotide synthesis. At the same time, the incorporation of phosphorothioate (PS) linkages—essential for therapeutic stability and efficacy—introduces diastereomeric complexity that challenges both manufacturing control and analytical characterization.

In this presentation, we highlight how advances in sequential enzymatic fragment synthesis and ligation—core capabilities of Codexis’ ECO Synthesis® Manufacturing Platform—address these limitations. By combining biocatalytic innovation, process optimization, and machine learning–guided design, this approach enables control over PS diastereomeric composition while enhancing ligation efficiency and reproducibility.

The result is a streamlined, scalable manufacturing strategy that improves downstream processing and delivers high-quality siRNA with superior consistency, purity, and performance.

• Leveraging best-in-class oligonucleotide chemistry and genetic insights to address obesity and cardiometabolic disorders
• The role of PN and stereochemistry in building differentiated clinical assets
• Beyond RNAi: RNA editing, bifunctional constructs, and pushing the boundaries on what is possible in RNA medicine

• Leveraging computational intelligence to transform RNA therapeutics: from target identification and molecular design to personalized treatment strategies for rare disease populations

• Bridging the gap between AI innovation and clinical reality: case studies in RNA drug development, regulatory considerations, and translational pathways to patient care

• Addressing barriers such as endosomal escape, immunogenicity, manufacturing scalability, cost-effectiveness, biodistribution optimization, and regulatory considerations that impact the clinical development and commercialization of targeted RNA medicines
• Future directions and therapeutic opportunities: exploring next-generation technologies including organ-specific targeting beyond the liver, CNS delivery strategies, intracellular compartment-specific localization, combination approaches, and expanding the therapeutic window to unlock new disease applications for oligonucleotide and RNA-based therapeutics