Optimizing mRNA Production: Achieving 25 g/L mRNA Yield with Low dsRNA by Integrating PAT

On-Demand Webinar

Listen to an in-depth exploration of mRNA manufacturing workflow, designed to enhance efficiency and scalability.

mRNA production requires DNA template as a critical raw material. In the webinar, discover an efficient purification process comprising scalable continuous in-line lysis, anion exchange chromatography (AEX) capture, and selective hydrophobic interaction chromatography (SHIC) for polishing supercoiled (sc)DNA. At-line monitoring of scDNA linearization ensures complete conversion in minimal time, optimizing reagent consumption.

DNA template is used in IVT production, which can be scaled from micrograms to multi-grams with rapid at-line PATfix monitoring of nucleoside triphosphate (NTP) consumption and mRNA production. A data-driven model of process yield can be derived to optimize reaction cost drivers, and minimize dsRNA formation - a critical quality attribute in mRNA products.

Our speaker will demonstrate how to achieve IVT yields of 25 g/L in batch mode and how to design an efficient fed-batch IVT reaction. He will also show how to optimize purification at µg-scale using multiparallel (96 well) and spin-based devices in Oligo dT and SDVB chemistries, and scale these methods to multi-mg levels for clinical manufacturing.

 

What You Will Learn:

  1. Achieve scalable preparation of high-quality DNA template
  2. Understand the use of at-line analytics to monitor the IVT reaction
  3. Couple PAT with DOE to increase yield of IVT to 25 g/L
  4. Use affinity chromatography for isolation of mRNA
  5. Remove dsRNA, residual DNA template and RNA fragments in scalable fashion



     

 

 

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