Researchers from Nagoya University have developed a novel synthesis technique to produce high-purity chemically synthesized mRNA. The technique can be used to accelerate vaccine development which is currently hindered by a slow enzyme reaction step.
The technique, published in Nucleic Acids Research, will hopefully lead to viral outbreak mitigation at a preliminary stage by allowing a more rapid reaction to viral outbreaks and emerging diseases.
Despite its popularity, especially given its significant role in combating the COVID-19 pandemic, mRNA production remains a challenge due to concerns surrounding production speed and purity. In their research, the team addresses both of these concerns by presenting a fully chemically synthesized mRNA.
"One of the most significant advantages of fully chemically-synthesized mRNA is its ability to bypass the complex and time-consuming enzymatic reactions typically required in mRNA production. A method that relies purely on chemical reactions would significantly shorten the production process," said Assistant Professor Masahito Inagaki.
To achieve chemically synthesized mRNA, the team developed a new phosphorylation reagent containing a nitrobenzyl group to serve as a hydrophobic purification tag.
"Nitrobenzyl groups have high hydrophobicity; therefore, when the nitrobenzyl group is introduced into the RNA molecule, the mRNA becomes more hydrophobic. As impure RNA lacks nitrobenzyl groups, it can be easily separated from the target RNA containing nitrobenzyl groups using reverse-phase high-performance liquid chromatography," Masahito Inagaki added.
"This approach yields pure RNA, free from length inconsistencies and impurities typically associated with transcription-based synthesis methods."
The breakthrough achieved by the team has significant implications for future medical treatments and vaccine development.
"This innovation paves the way for the highly efficient production of fully chemically synthesized mRNA and circular mRNA, which hold the potential to revolutionize RNA drug discovery and expand the scope of mRNA-based treatments," said Professor Hiroshi Abe.