phys.org
In a significant advancement for global health, researchers from Nagoya University in Japan have developed a revolutionary method to produce fully chemically synthesized mRNA. This technique eliminates the need for time-consuming enzymatic steps, promising faster vaccine production during viral outbreaks. The findings, published in Nucleic Acids Research, could transform the development of vaccines and treatments for infectious diseases, genetic disorders, and even cancer.
Traditional mRNA production relies on a mix of chemical synthesis and enzymatic reactions, the latter being a bottleneck due to its complexity and slower pace. The Nagoya University team, led by Professor Hiroshi Abe and colleagues, has introduced a new phosphorylation reagent containing a hydrophobic nitrobenzyl group. This reagent enables the production of high-purity mRNA through chemical synthesis alone.
Additionally, the researchers demonstrated the successful synthesis of pure circular mRNA, which lacks terminal structures and resists degradation by enzymes in the body. Circular mRNA’s stability could lead to longer-lasting therapeutic effects, enhancing its potential in future medical applications.
This breakthrough not only accelerates the production process but also resolves key challenges in mRNA purity. Impurities in mRNA have been associated with heightened immune responses, which can increase the risk of side effects, such as inflammation. The novel purification method, using reverse-phase high-performance liquid chromatography, separates impure RNA from target RNA with unprecedented efficiency.
The ability to rapidly produce high-purity mRNA is critical for responding to emerging viral threats. Faster vaccine development could mitigate outbreaks before they escalate into global pandemics. This advancement is particularly relevant in the wake of COVID-19, where mRNA technology proved instrumental in combating the virus.
Beyond infectious diseases, this innovation opens doors for broader applications of mRNA-based treatments, including therapies for cancer antigens and genetic diseases. Fully synthesized mRNA also benefits patients with strong immune reactions to vaccines by reducing the risk of adverse effects linked to impurities.
By addressing both speed and quality, the Nagoya University team’s work has the potential to revolutionize RNA drug discovery, paving the way for more efficient, scalable, and safer mRNA-based therapies.