KAIST

<(From Left) Professor Yong Woong Jun, Ph.D candidate Tae Ung Jeong, Ph.D candidate Jihun Choi>

mRNA, widely known from the COVID-19 vaccine, is not actually a “therapeutic agent,” but a technology that delivers the blueprint for functional proteins into the body so that induces therapeutic effects. Recently, its application has expanded to cancer and genetic disease treatments, but mRNA therapeutics have caused serious side effects such as pulmonary embolism, stroke, thrombosis, and autoimmune diseases because proteins are excessively produced all at once immediately after administration. Although technology to control the endogenous protein factory has been continuously needed, there had been no suitable solution.

KAIST (President Kwang Hyung Lee) announced on the 1st of December that Professor Yong Woong Jun’s research team in the Department of Chemistry has proposed a new strategy that can control the initiation timing and rate at which mRNA produces proteins. By using this method, the rate of protein production can be adjusted/personalized according to a patient’s condition, enabling safer treatment.

This technology is expected to serve as an important turning point in next-generation mRNA therapeutics, not only fundamentally reducing side effects of mRNA treatments but also enabling application to treatment areas requiring precise protein regulation such as stroke, cancer, and immune diseases.

For a protein to be produced, the cell’s “protein production machinery (ribosomes and initiation factors)” must attach to the mRNA blueprint and begin working. The research team focused on the fact that delaying this process even slightly can prevent the sudden surge of protein production.

Therefore, instead of using complex technologies, they developed a simple method in which intentionally slightly damaged DNA fragments are attached to mRNA. These DNA fragments act like a small “shield,” preventing the protein production machinery from immediately attaching to the mRNA and thereby gently slowing the initiation speed of protein production.

The damaged DNA used here is a safe biological material naturally recycled in the body and is very inexpensive. Because it only needs to be mixed with mRNA right before injection, it is suitable for real-world medical use.

As time passes, the body’s natural “repair enzymes” partially degrade the damaged DNA, and during this process, the structure attached to the mRNA is released, smoothly transitioning the protein production speed back to normal mode. As a result, the previous risk of proteins being explosively produced all at once is greatly reduced.

The research team confirmed that by adjusting the length and degree of damage of the DNA, they could precisely design when and how slowly protein production would begin. They also found that even when multiple types of mRNA are administered at once, the proteins can be produced sequentially in the desired order, meaning this method could innovate existing approaches that required multiple separate injections for complex treatments.

This technology was selected by KAIST as one of its “Future Promising Core Technologies” and was also introduced at the “2025 KAIST Techfair Technology Transfer Session.”

<A translation-control strategy based on DNA–mRNA hybrids. The damaged base (in red) is removed by a repair enzyme, after which the DNA and mRNA dissociate, allowing translation factors and ribosomes to bind and initiate protein translation>

Professor Yong Woong Jun said, “Biological phenomena are ultimately chemistry, so we were able to precisely control the protein production process through a chemical approach,” and added that “this technology not only enhances the safety of mRNA therapeutics but also provides a foundation for expanding into precision treatments tailored to various diseases such as cancer and genetic disorders.”

The results of this research, with Jihun Choi (KAIST, 3rd-year PhD student) and Tae Ung Jeong (KAIST, 1st-year PhD student) participating as co–first authors, were published on November 6 in Angewandte Chemie International Edition, one of the most prestigious journals in the field of chemistry.
 ※ Paper title: “Harnessing Deaminated DNA to Modulate mRNA Translation for Controlled and Sequential Protein Expression,” Authors: Jihun Choi (KAIST, co–first author), Tae Ung Jeong (KAIST, co–first author), and Yong Woong Jun (KAIST, corresponding author), among a total of 10 authors, DOI: 10.1002/anie.202516389

This study was supported by the National Research Foundation of Korea (NRF) through the Excellent Young Researcher Program.