Main Conference – Day 1Wednesday, 18 March 2026 - CET (Central European Time, GMT+01:00)

• RNA modifications play a critical role in influencing RNA structure and function, yet traditional prediction methods often fail to account for these molecular marks.
• The ViennaRNA Package introduces an advanced approach to RNA structure prediction by integrating modified nucleotides through custom alphabets, tailored energy parameters, and adapted folding algorithms.
• Experimental data on modified bases is incorporated into the prediction process, enhancing the accuracy of RNA structure modeling.
• Case studies highlight the improved prediction accuracy for known modified RNAs, demonstrating the effectiveness of this approach in addressing challenges associated with modified RNA structure analysis.

Manufacturing success of RNA therapeutics depends on precise control of quality of raw materials, in vitro transcription (IVT) reaction conditions and purification strategies that apply across constructs. The presentation will outline a conceptual framework for mRNA and saRNA production that integrates rapid at-line analytics to monitor IVT kinetics, enabling data-driven endpoint selection and feed strategies that raise yield and batch-to-batch consistency. A Quality by Design approach maps critical IVT factors—NTP/Mg2+ ratio, polymerase selection, temperature and time, template design, and capping strategy—to critical quality attributes (CQAs) and cost, defining a robust design space that optimizes productivity without compromising quality.

Downstream processing requires scalable, high recovery purification tools and techniques that effectively remove double-stranded RNA, RNA fragments, residual reaction components (NTPs, T7), to reduce immunogenicity and increase cellular potency for both mRNA and saRNA. Affinity, multimodal and reverse-phase chromatography each offer technical advantages and practical challenges that have to be understood and managed in manufacturing environments.

Universal requirements (integrity, dsRNA burden, residuals) and format-specific needs (capping for mRNA; long-transcript handling and hydrolytic potential of saRNA) demand decision frameworks for selecting appropriate IVT strategies and purification approaches. The ultimate goal is a manufacturing approach that scales efficiently and accelerates onboarding of new RNA constructs—translating bench-top control into reliable, multi-product production platform.

• Characterisation of mRNA critical quality attributes using LC MS
• Automated online direct mRNA sequencing mapping using partial RNase T1 digests
• Analysis of mRNA multimerisation (aggregation) using ion-pair reversed phase HPLC

• Addressing scalability challenges with a continuous manufacturing platform: the same equipment and recipe from pre-clinical to commercial and from individualized medicines to epidemic vaccines.
• Accelerating mRNA Therapeutics Development Through Mechanistic Process Modeling: focus on a mechanistic IVT performance model that predicts reaction kinetics and the two key CQAs that are directly linked to mRNA functionality: capping efficiency and intactness.
• Cost reduction without compromising quality: cases studies of mRNA and saRNA will be presented with CQA data, targeted capacities and costs.