Damaged DNA as a “Shield”: A New Way to Control mRNA Therapy

mRNA therapy has rapidly become one of the most promising technologies in modern medicine. Instead of directly injecting proteins into the body, scientists can inject mRNA, allowing cells to produce therapeutic proteins themselves.

However, once injected into the body, the rate of protein synthesis becomes uncontrollable because a large number of mRNA molecules are introduced at once. Therefore, numerous ribosomes bind to different parts of the mRNA simultaneously, resulting in a rapid spike of protein production. This leads to severe side effects, such as stroke and autoimmune diseases. 

A research team led by Professor Jeon Yong Woong at the Department of Chemistry at KAIST has developed a brilliant solution to this problem. 

The researchers purposely mixed damaged DNA with the mRNA before injection. When damaged DNA binds to mRNA, it temporarily interferes with translation. Instead of ribosomes immediately translating the entire mRNA sequence, DNA repair enzymes must first remove the damaged DNA before normal translation can resume. This slows down and regulates protein synthesis, preventing the dangerous burst of protein production seen in conventional mRNA therapies. 

What exactly is “Damaged DNA”?

Damaged DNA, also referred to as deaminated DNA, is created by replacing the thymine base with uracil within the DNA strand. The damaged DNA is repaired via Base Excision Repair, where the key enzyme Uracil-DNA glycosylase removes the abnormal uracil base, making the DNA structure become unstable and finally detach from the mRNA. This allows normal translation to resume.

How does this control protein synthesis?

The damaged DNA can bind to different regions of the mRNA, but the strongest inhibition occurs near the 5′ cap and the 5′ untranslated region, where translation initiation factors normally bind. Therefore, translation is temporarily inhibited and then gradually restored once the damaged DNA is removed by repair enzymes. This allows all the necessary proteins to eventually be produced, but at a safer and more controlled rate. 

What are the advantages?

One advantage of this technology is its ability to precisely regulate protein production rather than simply slowing it down. By adjusting the degree of damage and the length of damaged DNA, researchers can control exactly when protein synthesis begins and how gradually it progresses. Additionally, multiple mRNAs can be programmed to produce proteins in a specific sequence, allowing for more complex multi-step therapies.

Another major advantage is that the damaged DNA is biologically compatible, inexpensive, and easy to use. The DNA fragments can simply be mixed with mRNA immediately before injection without requiring complicated steps. Unlike earlier mRNA technologies that relied on toxic chemicals or external stimulation, this method uses the body’s own repair mechanisms. This makes the technology especially promising for future medicine applications.

Professor Jeon says, “Biological processes are ultimately controlled by chemistry. Through a chemical approach, we were able to precisely regulate protein synthesis.”

---

Citations

“최신 연구성과 | KAIST 화학과.” Kaist.ac.kr, 2025, chem.kaist.ac.kr/research_results/view/id/2625#u. Accessed 23 May 2026.

Harnessing Deaminated DNA to Modulate MRNA Translation for Controlled and Sequential Protein Expression. 6 Nov. 2025, fangrna.lab.westlake.edu.cn/js/2025_ACIE.pdf.