A groundbreaking study from South Korea has uncovered a game-changing secret for mRNA stability, potentially revolutionizing RNA-based vaccines and therapeutics. Led by Professors V. Narry Kim and Jin-Hong Kim, the research team has identified a series of viral RNA motifs that make conventional mRNA far more stable and efficient, opening up new possibilities for RNA drug manufacturing.
The key to this discovery lies in viral RNA motifs, including the A7 motif, which can make linear mRNA as stable as circular RNA. This stability boost translates to higher protein expression and the ability to produce durable, manufacturable RNA drugs. The study, published in Nature Biotechnology, reveals that these motifs protect mRNA from rapid degradation by recruiting the host enzyme TENT4, which extends the poly(A) tail, a molecular safeguard that stabilizes RNA and sustains protein production over time.
Among the 11 newly identified motifs, the A7 motif stands out. It made linear mRNA as stable as circular RNA while achieving even higher protein translation levels. In preclinical mouse-liver studies, A7-modified mRNA maintained robust protein expression for more than two weeks, outperforming comparable circular RNA constructs. This discovery is the result of a close collaboration between Narry Kim’s laboratory at Seoul National University and Jin-Hong Kim’s team at the Institute for Basic Science (IBS) in Daejeon.
The two groups combined expertise in RNA biochemistry, viral genomics, and biotechnological engineering to systematically identify RNA elements capable of boosting stability without compromising translation or manufacturability. "By learning from nature’s own viral RNA design principles, we have found a way to make linear mRNA both stable and highly expressive," said Professor Jin-Hong Kim, emphasizing that the motifs are compatible with N1-methylpseudouridine, a key chemical modification used in current mRNA vaccines to enhance efficacy and reduce immunogenicity.
This breakthrough overcomes a long-standing limitation in RNA medicine. The intrinsic instability of mRNA has long limited its use in vaccines and therapeutics. While alternative formats such as circular RNA or self-amplifying RNA offer greater persistence, they often suffer from reduced translation efficiency, modification incompatibility, and complex manufacturing. The Korean team’s findings provide a simple, modular solution: small RNA elements that naturally stabilize linear mRNA while keeping production processes straightforward and scalable.
The implications of this discovery are far-reaching. By incorporating these viral stability motifs—particularly A7—future RNA vaccines and therapeutics could achieve high, long-lasting protein expression, low immune activation, and cost-effective manufacturing. This positions South Korea as a global leader in RNA innovation and could accelerate the next generation of RNA-based drugs worldwide. "This breakthrough opens a new chapter for RNA medicine," commented Professor Narry Kim. "It allows us to combine the durability of circular RNA with the flexibility and simplicity of linear mRNA."
