mRNA vaccines against epidemics can be synthesized in less time using a new technique

At a time when viral outbreaks can escalate into global pandemics with alarming speed, the ability to rapidly develop new vaccines has become crucial. However, the speed of vaccine production is limited because the mRNA used is partly synthesized chemically and partly using enzymes, a relatively slow process.

A team of researchers from Nagoya University in Japan has successfully developed an innovative synthesis technology capable of producing high-purity, fully chemically synthesized mRNA, eliminating slower enzymatic reactions.

This advancement lays the foundation for faster responses to viral outbreaks and emerging diseases, which will hopefully mitigate future infections at an early stage. Their results were published in the journal Nucleic acid research.

Given its important role in combating the COVID-19 pandemic, mRNA is now widely recognized for its potential to prevent infectious diseases. Experts predict that in the future, mRNA technology will be used to treat genetic disorders and emerging diseases. However, mRNA production remains difficult due to concerns over purity and production speed.

These problems can be solved using fully chemically synthesized mRNAs. According to Masahito Inagaki, “one of the most important 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 solely on chemical reactions would significantly reduce production. process.”

It also provides benefits to people who have a strong immune response to vaccines. mRNA derived from 5′-monophosphorylated RNA is likely to be contaminated with incomplete RNA fragments, causing a strong immune reaction. This immune response increases the risk of side effects, including inflammation. However, existing purification technologies have struggled to remove these impurities, limiting their potential.

To address these issues, Professor Hiroshi Abe, doctoral student Mami Ototake, and Assistant Professor Inagaki designed a new phosphorylation reagent with a nitrobenzyl group that serves as a hydrophobic purification label.

Inagaki explained: “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 target RNA containing nitrobenzyl groups using the reverse method. High-performance liquid chromatography in phase.

“This approach produces pure RNA, free of length inconsistencies and impurities typically associated with transcription-based synthesis methods.”

In addition to chemically synthesizing the mRNA, the team also created pure circular mRNA using the same method. Circular mRNAs are unique because they lack terminal structures, making them resistant to degradation by nucleic acid-degrading enzymes in the body, resulting in a longer-lasting medicinal effect.

The breakthrough in mRNA production has significant implications for the future of medical treatments. “This innovation paves the way for the highly efficient production of fully chemically synthesized mRNAs and circular mRNAs, which have the potential to revolutionize RNA drug discovery and expand the scope of RNA-based therapeutics. mRNA,” Abe said.

Faster, purer vaccine production should improve our response times to future infectious threats. In the future, the team also hopes to use these results to develop new mRNA vaccines against cancer antigens and genetic diseases.