Creating mRNA with an all-chemical process may allow for customized mRNA vaccines

Researchers at Nagoya University in Japan have developed a new chemical-only process that may represent an important breakthrough in creating 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. These 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, current vaccines that use biological processes do not allow for the precise molecular design of mRNA, which limits their use in creating new vaccines as variants emerge.

Research group led by Professor Hiroshi Abe and Associate Professor Naoko Abe of the Graduate School of Science at Nagoya University has developed the first completely chemical synthesis method for mRNA. In their study, the group synthesized a part of the mRNA called the cap. The cap is important because it promotes the translation of mRNA into proteins and protects mRNA from degradation.

To prepare synthetic mRNA, such as that used in vaccines, the two currently used biological methods rely on enzymes to incorporate the cap structure into the mRNA. However, the researchers found that their technique could synthesize a variety of chemically modified mRNA strands with a cap structure.

Professor Hiroshi Abe says, "Our research suggests that it is possible to make mRNAs with precisely introduced chemical modifications with complete control over the process. The molecular design reported in our study exhibits five times higher translational activity than that of enzyme-produced natural-type mRNA. This means that mRNA can be synthesized in large quantities at low cost using chemical synthesis."