Easy to remove tag could make mRNA synthesis for vaccines quicker and cheaper

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Source: © Christoph Burgstedt/Science Photo Library

Chemical synthesis takes another step towards overtaking more complex enzymatic routes

A new hydrophobic tag enables the high-purity production of a key intermediate in the chemical synthesis of capped mRNA and circular RNA. These RNAs are used in research and therapeutics such as mRNA vaccines and are normally expensive to make because of the way they are produced.

RNA for therapeutic purposes is typically synthesised enzymatically via in vitro transcription or, more recently, using chemical synthesis. The latter allows for the introduction of precise chemical modifications to enhance translational activity, is more easily scalable and is faster than enzymatic methods. ‘In order to produce mRNA through transcription, it would take more than a month to synthesise the template DNA,’ explains Hiroshi Abe of Nagoya University, Japan, who led the work. ‘On the other hand, the chemical synthesis method for mRNA can significantly reduce production time by skipping the synthesis of the DNA template.’ Both RNA synthesis methods produce 5’-monophosphate, the in demand intermediate to make mRNA, but also 5’-triphosphate RNA that is difficult to separate out and impedes further reactions.