KAIST: Suppressing mRNA Therapeutic Side Effects... Immunotherapy for Stroke and Cancer

A new approach has been proposed to suppress the side effects of messenger ribonucleic acid (mRNA), opening up possibilities for its application in immunotherapy for stroke and cancer.

KAIST announced on December 1 that a research team led by Professor Jeon Yongwoong of the Department of Chemistry has discovered a new strategy that enables control over both the initiation point and the speed at which mRNA produces proteins.

(From left) Professor Jeon Yongwoong of KAIST, doctoral candidates Tae Woong Jung and Jihoon Choi. Courtesy of KAIST

mRNA therapeutics deliver genetic information that enables the human body to directly produce needed proteins. This technology gained attention during the COVID-19 pandemic due to its rapid and robust protein expression capabilities.

However, the rapid and excessive production of proteins in a short period, along with sudden biological responses, has left unresolved side effects such as pulmonary embolism, stroke, thrombosis, and autoimmune diseases.

The strategy proposed by the research team is expected to become an important turning point in the development of next-generation mRNA therapeutics, as it can fundamentally reduce side effects and be applied to treatment fields that require precise protein regulation, including stroke, cancer, and immune diseases.

For proteins to be produced, the 'protein manufacturing machinery' (ribosomes and translation factors) within cells must attach to the mRNA blueprint and begin their work. The research team focused on the fact that delaying this process can prevent the sudden, mass production of proteins.

For this reason, they developed a simple method that attaches intentionally damaged DNA fragments to mRNA, instead of using complex technologies. These DNA fragments act as small 'shields,' preventing the protein manufacturing machinery from immediately attaching to the mRNA and gently slowing the initiation of protein synthesis.

These damaged DNA fragments are safe biomaterials that are naturally recycled within the body, are inexpensive, and can be mixed with mRNA just before injection, making them suitable for practical use in medical settings.

Notably, over time, the body's 'repair enzymes' naturally restore the damaged DNA, and during this process, the structure attached to the mRNA is released, returning the protein synthesis speed to normal. According to the research team, this greatly reduces the risk of explosive, simultaneous protein production seen in existing methods.

This technology was selected as one of KAIST's 'Future Promising Source Technologies' and was also introduced at the '2025 KAIST Techfair Technology Transfer Conference.'

Professor Jeon stated, "Biological phenomena are ultimately governed by chemistry, so we were able to precisely control the protein production process through a chemical approach. The technology developed by our team will not only enhance the safety of mRNA therapeutics but also lay the foundation for customized precision treatments for various diseases such as cancer and genetic disorders."

Meanwhile, Jihoon Choi and Tae Woong Jung, doctoral candidates in the Department of Chemistry at KAIST, participated as co-first authors in this research. The results were recently published in the chemistry journal 'Angewandte Chemie International Edition.'

This content was produced with the assistance of AI translation services.