As described in the journal ACS Chemical Biology, researchers at Nagoya University in Japan have developed a new chemical-only process that may enabled the creation of customized mRNA vaccines for a variety of diseases and allow for the inexpensive preparation of mRNA in large quantities.

During the COVID-19 pandemic, mRNA vaccines were successfully used to boost immunity. Such vaccines teach cells how to make a protein that triggers the body’s immune response, allowing its natural defenses to recognize the invading virus. However, these current vaccines use biological processes which do not allow for the precise molecular design of mRNA; this limits their use in creating new vaccines as variants emerge.

In order to prepare synthetic mRNA, such as that used in vaccines, two biological methods are currently used. These rely on enzymes to incorporate the so-called “cap structure” into the mRNA. However, the Japanese researchers found that their technique could synthesize a variety of chemically modified mRNA strands with a cap structure.

This research suggests that it is possible to make mRNAs with precisely introduced chemical modifications with complete control over the process. Notably, the molecular design produced by this process demonstrated five times higher translational activity than that of enzyme-produced mRNA. This means that mRNA can be synthesized in large quantities at low cost using chemical synthesis.

Chemically modified mRNA could be used to create customized vaccines against a variety of infectious diseases including viruses and cancers. By introducing these chemical modifications, the mRNA becomes stable. This could allow for the creation of long-lasting and effective mRNA vaccines. In addition, it could allow mRNA to be administered directly instead of using lipid nanoparticles, which are used for delivery in current vaccines.

One of the exciting implications of this research is that it could be used in the next generation of vaccines. And the researchers hope that the capping method reported here will be of great use in the development of new RNA therapeutics.

- ACS CHEMICAL BIOLOGY, May 24, 2022, “Complete chemical synthesis of minimal messenger RNA by efficient chemicalcapping reaction,” by Naoko Abe, et al. © 2022 American Chemical Society. All rights reserved.