KAIST "Increasing Possibility of Developing Low-Dose, High-Efficiency RNA Vaccines"

Research results facilitating the development of low-dose, high-efficiency ‘RNA vaccines’ have emerged from domestic researchers.

KAIST announced on the 23rd that Professor Kim Yoon-ki’s research team in the Department of Biological Sciences at KAIST has identified a new mechanism of protein synthesis involving circular RNA occurring inside eukaryotic cells.

Comparison of Circular RNA and Linear RNA. Provided by KAIST

According to KAIST, the currently widely used coronavirus mRNA vaccines utilize linear mRNA, which exhibits very unstable characteristics inside cells.

In contrast, circular RNA is much more stable than linear RNA, and many domestic and international pharmaceutical companies are developing circular RNA to enhance RNA stability. For the same reason, recently, there has been growing interest in techniques that can maximize RNA stability and synthesis efficiency related to mRNA vaccines.

Because linear mRNA is very unstable within cells, high doses of mRNA administration are inevitable to increase antibody production efficiency. However, high-dose administration reveals problems causing side effects attributed to mRNA.

In this context, the research team attracted attention by identifying a new form of protein translation occurring in circular RNA. The key to this discovery is that most circular RNAs generated inside cells carry the exon junction complex (EJC).

It was revealed that the exon junction complex directly binds to a protein (eIF3g) that functions to recruit ribosomes responsible for protein synthesis, ultimately attracting ribosomes and inducing protein synthesis.

This is significant as it is the first time the binding between the exon junction complex and the eIF3 complex has been proposed, revealing cap-independent protein translation mediated by the exon junction complex, which was previously unknown.

In particular, the cap-independent protein translation mediated by the exon junction complex has the advantage of enabling protein translation in forms of RNA without a cap structure, including circular RNA, beyond traditional linear mRNA-based therapeutics.

The research team’s achievement also lies in uncovering a new protein translation mechanism that overcomes the limitations of circRNA, which, while more stable than traditional mRNA-based therapeutics, has lower protein translation efficiency, thereby expanding the efficiency and application of circRNA-based therapeutics.

This study, co-first authored by Jang Ji-yoon and Shin Min-kyung, doctoral students in the Department of Biological Sciences at KAIST, and Park Ju-ri, was conducted with support from the National Research Foundation of Korea and was recently published in the international journal Nucleic Acids Research.

Professor Kim Yoon-ki explained, “This study is meaningful in that it elucidated the synthesis process occurring in highly stable circular RNA,” adding, “By utilizing this mechanism, it is expected that mRNA vaccines capable of high stability and high-efficiency protein synthesis can be developed while minimizing side effects.”

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