As mRNA-based therapeutics move beyond early vaccine successes to encompass diverse modalities, the expectations for manufacturers to deliver products with consistent purity and quality are rising. To that end, traditional purification and quantitation processes will need to evolve to address current and new manufacturing challenges. Specifically, immunogenic double-stranded RNA (dsRNA) byproducts are a major impurity complicating the purification of RNA-based vaccines and therapeutics consisting of mRNA, circRNA, or saRNA. In addition, current UV methods of nucleic acid quantitation require extra sample handling in the form of dilutions, which can lead to inaccuracies in measuring mRNA concentration.

In this GEN webinar, Rice University assistant professor Kelsey Swingle, PhD, will provide a current overview of mRNA lipid nanoparticle therapeutics and Repligen senior scientist Nathaniel Clark, PhD, will discuss emerging purification and quantitation techniques that work for the new generation of mRNA therapeutics beyond COVID-19 vaccines. Key learnings from the webinar include:

• Size determination quantification of dsRNA contaminants
• A dsRNA-specific affinity chromatography resin that removes dsRNA byproducts and eliminates the immune response in cell-based assays
• Validation of variable pathlength technology for accurate, reproducible mRNA quantitation
• Potential of in-line variable pathlength technology to improve mRNA manufacturing

A live Q&A session followed the presentation, offering a chance to pose questions to Dr. Clark.

Produced with support from: