The messenger ribonucleic acid (mRNA) vaccine technology that saved humanity from the novel coronavirus infection (COVID-19) is expanding its scope to the treatment of cancer, genetic disorders, and autoimmune diseases. However, there has been a problem of not being able to accurately identify diseased cells and the treatment effect not lasting long. Japanese researchers found clues to solve these issues by altering the form of mRNA.
Researchers from Nagoya University in Japan said on the 19th in the international journal "Nature Biotechnology" that they found a method for mRNA therapies injected into the human body to synthesize therapeutic proteins exclusively in cancer cells.
Living organisms transfer genetic information for specific proteins to mRNA to produce the desired proteins. Ultimately, the more protein the administered mRNA produces, the greater the therapeutic effect. If the protein synthesis efficiency is low, the therapeutic effect diminishes, necessitating frequent administration of the mRNA therapy.
The researchers used circular mRNA, which is more stable than linear mRNA used in existing mRNA therapies. Linear mRNA is easily broken down by enzymes in the body, whereas circular mRNA is relatively stable due to the absence of terminal structures. This allows for long-term protein synthesis. This means that treatment effects can be sustained for a long time with just one administration.
The problem is that circular mRNA has a lower protein synthesis efficiency than linear mRNA. To address this limitation, the researchers developed a method of introducing a cap structure to the circular mRNA itself. The cap aids in protein production and prevents the mRNA from being destroyed. By inserting the cap structure, which was only present in linear mRNA, into circular mRNA, the researchers increased the protein synthesis efficiency. The circular mRNA with a cap could synthesize up to 200 times more protein while maintaining stability for an extended period compared to existing methods, the researchers noted.
The researchers tested the new circular mRNA on human liver cancer cells. This mRNA was designed to instruct protein synthesis upon detecting specific RNA that is abundantly produced only in liver cancer cells. The results showed that the mRNA did not operate in normal cells, leading to no changes, but in liver cancer cells, the amount of protein synthesized increased more than 50 times. This indicates that it can selectively exert therapeutic effects only in cancer cells without affecting normal cells.
The researchers noted that using this technology allows therapeutic proteins to be synthesized only in diseased cells, minimizing side effects while effectively treating diseases.
Abe Hiroshi, a professor at Nagoya University, said, "Currently used mRNA drugs are unstable and require repeated injections, but the technology developed this time can address these issues. By utilizing this technology, it is possible to design mRNA therapies to produce toxic proteins only in cancer cells, inducing the self-destruction of cancer cells."
References
Nature Biotechnology (2025), DOI: https://doi.org/10.1038/s41587-025-02561-8