There is a common side effect that most people experience after receiving a messenger ribonucleic acid (mRNA) vaccine. It is an inflammatory reaction that causes swelling or pain in the arm and symptoms of body aches after vaccination. Recently, technology has been developed to reduce this.
Researchers at the University of Pennsylvania developed an mRNA delivery technology that reduces side effects of the mRNA vaccine while enhancing its effectiveness, and published their findings in the international journal Nature Biomedical Engineering.
The key to the research is changing the composition of 'ionizable lipids,' which are the main components of 'lipid nanoparticles (LNP)' that act as the delivery system for the vaccine. Ionizable lipids are lipids that change states according to acidity (pH) and facilitate the entry of mRNA into cells. Until now, ionizable lipids have been synthesized primarily through reactions that combine two substances to create new molecules.
Professor Gong Ningchang from the University of Science and Technology of China, who participated in the study, noted, "Since the existing synthesis methods have been very successful, there hasn't been much effort to find alternatives."
The research team created hundreds of new structures of ionizable lipids using the 'Mannich reaction' discovered 100 years ago. The Mannich reaction is a method of combining three substances to produce molecules of various structures.
Experimental results showed that adding 'phenolic groups,' which are combinations of hydrogen and oxygen, to the lipids significantly reduced inflammation and improved immune responses.
Phenol is a component found in antioxidant foods such as olive oil and green tea, which inhibits reactive oxygen species that damage cells. The research team explained, "Compounds containing phenol neutralize the effects of 'free radicals' that can disrupt the body's chemical processes," adding, "As a result, it leads to a reduction in inflammation." Free radicals are molecules that have unpaired electrons.
The mRNA vaccine using this lipid did not simply reduce side effects. When creating the novel coronavirus disease (COVID-19) vaccine, the immune response was over five times stronger than before, and the tumor reduction effect in cancer treatment vaccines was three times higher. Additionally, experiments treating genetic diseases using gene editing techniques showed more than double the effectiveness compared to previous methods.
Michael J. Mitchell, a professor at the University of Pennsylvania, emphasized, "A chemical reaction from a century ago changed cutting-edge medical technology," stating, "If we continue to rediscover forgotten chemical technologies, more medical breakthroughs could be unlocked."
References
Nature Biomedical Engineering (2025), DOI: https://doi.org/10.1038/s41551-025-01422-8