Korean researchers have developed a technology that induces stronger immune responses at lower doses than conventional mRNA vaccines, improving efficiency while reducing side effects.
A research team led by Dr. Cha Hyun-ju at the Nucleic Acid Therapeutics Research Center of the Korea Research Institute of Bioscience and Biotechnology (KRIBB) announced on July 1 that it has established a design method for a low-dose, high-efficiency mRNA vaccine platform.
mRNA vaccines, widely known from their use against COVID-19, work by delivering mRNA carrying the design information for an antigen protein into cells, prompting the cells to directly synthesize the protein and thereby inducing an immune response. They are considered next-generation vaccines due to their fast development speed and strong immune efficacy.
However, these vaccines have had drawbacks: they require relatively large doses, and higher doses can increase side effects such as fever and pain. Because mRNA is easily degraded in the body and cannot pass through cell membranes on its own, securing nanoparticle technology that safely encapsulates and transports mRNA into cells has also been a key challenge.
To overcome these limitations, the research team simultaneously improved lipid nanoparticles that deliver mRNA effectively into cells and the genetic design structure that helps mRNA function more efficiently.
The lipid nanoparticles were newly developed during this study. After comparing 96 candidate substances, the team confirmed that a new substance called "H9T6" delivers mRNA more effectively than existing materials. Notably, the new nanoparticles also help mRNA escape from endosomes — small pouch-like compartments inside cells — before being trapped and degraded. As a result, protein expression levels increased, strengthening the immune response.
The team also optimized the mRNA design itself. mRNA contains untranslated regions (UTRs) that determine protein production levels and stability. The researchers analyzed hundreds of thousands of candidates to identify the most effective structure, significantly boosting protein production capacity.
When the team applied the newly developed technology, it confirmed that strong antibody responses and immune responses occurred simultaneously even at lower doses than conventional vaccines. Safety tests (toxicity evaluations) simulating repeated vaccinations also showed no significant side effects, with only temporary reactions followed by recovery.
