Dr Serge RUCOLO

Process Research and Development, Merck & Co., Inc., Rahway, NJ, USA

Abstract: Since the emergence of mRNA vaccines as the lead prevention treatment against COVID-19, significant efforts have been made towards strengthening supply chains of the components necessary for their production to improve pandemic preparedness. Nucleoside triphosphates (NTPs), the elementary building blocks of mRNA, are key vaccines raw materials, but are not considered commodity chemicals and therefore pose a supply risk. Leveraging our existing bioelectrochemical oxidative phosphorylation platform, we have devised biocatalytic cascades to generate four essential NTPs necessary for mRNA vaccine production. We demonstrated the generation of NTPs from the corresponding cheap and readily available nucleosides in a one-pot process with minimal downstream purification. The NTPs generated from this method were then used to produce mRNA strands with comparable quality to those made with commercially available reagents, thereby offering an alternative supply for these essential mRNA building blocks.