In her presentation, May Guo, the Chief Commercial Officer of Synthgene, discussed the development of novel cap analogues and modified nucleoside triphosphates (NTPs) to enable therapeutic mRNA development. She began by explaining the structure of mRNA, highlighting the importance of the 5’ cap in initiating protein translation, recognising self versus non-self, and maintaining mRNA stability. Guo described two processes for adding the cap to mRNA: one-pot co-capping and enzymatic capping, noting that one-pot co-capping was simpler, produced fewer impurities, and was more cost-effective.
Guo detailed the steps involved in enzymatic capping and the differences between cap 0, cap 1, and cap 2, emphasising that cap 1 was commonly used in higher eukaryotes. She mentioned that cap analogues had been studied since the 1970s and discussed various types, including ARCA (anti-reverse cap analogue) and clean cap, which were used in vaccines like the Pfizer COVID-19 vaccine. Guo introduced several novel cap analogues developed by her team, such as UNA, ENE, and LNA, and explained their AI-assisted design process.
The presentation included results from in vitro and in vivo studies, showing that the new cap analogues had high capping efficiency and resistance to decapping enzymes. Guo highlighted the potential applications of these analogues in therapeutic mRNA development, particularly for proteins requiring long-lasting expression. She also discussed the biosafety of the analogues, noting that they performed well in animal studies without causing adverse effects.
Guo concluded by emphasising the importance of supporting clinical and commercial mRNA manufacturing with high-quality raw materials and mentioned Synthgene's GMP manufacturing facility and quality control measures. She also highlighted the company's commitment to helping customers fill gaps in their skills and accelerate their clinical development processes. The presentation ended with an invitation for questions from the audience.
