Evaluation of current and advanced analytical technologies for the comprehensive characterization of mRNA and its impurities

 

Evaluation of current and advanced analytical technologies for the comprehensive characterization of mRNA and its impurities


Wednesday 17th April 2024
4:30 PM CET

Speaker: Axel Guilbaud, Principal Scientist, Genentech
Intro: Birgit Rogell, Regional Product Manager mRNA Raw Materials Portfolio, Roche CustomBiotech

Topics to be covered:

  • Versatile Platform: In vitro transcribed mRNA is versatile for biotechnological applications
  • Therapies and Vaccines: Ideal for mRNA-based cancer therapies and vaccines
  • Impurity Concerns: Potential impurities during IVT production may affect safety and efficacy
  • Comprehensive Profiling: Pioneering study on IVT mRNA impurities using current and advanced analytical tools
  • Advanced Characterization: Utilizes techniques like ion-pair reversed-phase liquid chromatography, capillary gel electrophoresis, mass photometry, and native mass spectrometry for precise mRNA and its impurities- analysis.

In vitro transcribed (IVT) mRNA offers versatility in various biotechnological applications. Its rapid and cost-effective production makes it an attractive choice for mRNA-based cancer therapies and vaccines. However, the impurities generated during production can impact safety and efficacy.

This study pioneers a comprehensive profiling of IVT mRNA impurities using current and advanced analytical tools. We developed efficient ion-pair reversed-phase liquid chromatography (IP-RPLC) and capillary gel electrophoresis (CGE) methods for purity determination. Microcapillary electrophoresis was introduced for high-throughput mRNA impurity profiling. 

Our findings reveal impurities attributed to mRNA variants with different poly(A) tail lengths and the presence of double-stranded mRNA (dsRNA) by-products, particularly the dsRNA 3’- loop back form. Mass photometry and native mass spectrometry were implemented for accurate characterization of mRNA and its impurities, providing valuable information on identity and integrity. 

This study highlights opportunities for improving the analytical characterization of IVT mRNA, contributing to the refinement of mRNA production for biotechnological applications.

 

Register to join