RNA Leaders Europe

Abstract:

Production of mRNA vaccines and therapeutics with in vitro transcription (IVT) reaction can result in generation of double-stranded RNA (dsRNA), which is immunogenic and can compromise mRNA efficacy and safety. We introduce a novel dsRNA removal technique that selectively destabilizes dsRNA by targeting hydrogen bonding that is critical for dsRNA stability. After denaturation, contaminating RNA strands are removed with an established purification platform based on Oligo dT affinity chromatography. By only modulating the pH, this method enables controlled denaturation of dsRNA under non-hazardous conditions. This approach enhances the removal of dsRNA contaminants, increases mRNA integrity and reduces immunogenicity while offering a scalable, high-recovery alternative to traditional dsRNA purification methods, which suffer from low recovery and low selectivity, thereby improving the overall quality, safety, and manufacturability of mRNA products.