2 weeks Ago By Korea Bizwire
mRNA technology, which gained global prominence during the COVID-19 pandemic, instructs cells to produce specific proteins by delivering synthetic RNA sequences. (Image courtesy of Pixabay/CCL) SEOUL, April 4 (Korea Bizwire) — In a scientific breakthrough that could shape the next generation of vaccines and gene therapies, South Korean researchers have, for the first time, uncovered the precise mechanisms by which messenger RNA (mRNA) vaccines operate inside human cells. The discovery, published this week in the journal Science , comes from a team led by Dr.
V. Narry Kim of the Institute for Basic Science (IBS), and is being hailed as a foundational advancement for improving the effectiveness and safety of mRNA-based treatments. mRNA technology, which gained global prominence during the COVID-19 pandemic, instructs cells to produce specific proteins by delivering synthetic RNA sequences.
While its potential has extended into cancer vaccines, immunotherapies, and genetic medicine, the detailed workings of how therapeutic mRNA enters cells and is processed had remained poorly understood—until now. The IBS team used CRISPR-based knockout screening to eliminate individual genes in human cells and observe how those changes affected the uptake and translation of fluorescent protein-coding mRNA. The technique enabled the researchers to identify which proteins play key roles in the delivery, activation, and degradation of mRNA.
They discovered that heparan sulfate , a glycoprotein on cell surfaces, helps mRNA-containing lipid nanoparticles (LNPs) enter cells. Once inside, a proton pump enzyme (V-ATPase) acidifies the endosomal environment, temporarily disrupting the membrane to release mRNA into the cytoplasm, where protein expression begins. Crucially, the team also identified the protein TRIM25 as a gatekeeper that detects and destroys foreign RNA.
Activated by the same proton signals used to release mRNA, TRIM25 rapidly degrades unmodified RNA. However, the study clarified why a key modification used in COVID-19 vaccines— N1-methylpseudouridine —helps stabilize the RNA: the modified base weakens TRIM25’s ability to bind and destroy the mRNA, enhancing both durability and efficacy. V.
Narry Kim, Distinguished Professor of Biological Sciences at Seoul National University and Director of the RNA Research Division at the Institute for Basic Science (IBS), speaks at a press briefing on April 2 at Seoul National University in Gwanak District, Seoul, regarding her team’s world-first discovery of the cellular mechanisms behind mRNA vaccine function. (Yonhap) “This is the first time we’ve been able to explain what exactly happens inside cells when an mRNA vaccine is administered,” said Dr. Kim during a press briefing at Seoul National University earlier this week.
“Previously, it was assumed therapeutic mRNA would behave like native RNA, but this was never directly studied.” Kim emphasized the broader implications of the findings. “By identifying both the delivery enhancers and the molecular barriers, we can now design more efficient and safer mRNA therapeutics,” she said.
The research also opens new directions for immunology and cellular signaling, with the novel finding that proton gradients within cells can vary locally , adding complexity to how immune defenses are activated. The first author, Dr. Myunghwan Kim, has already transferred parts of this technology to the Korea Disease Control and Prevention Agency (KDCA), and joint work is underway with the International Vaccine Institute to develop even more stable vaccines.
As mRNA platforms continue expanding beyond infectious diseases into cancer and rare genetic disorders, this foundational understanding may prove critical for the next wave of biomedical innovation. With scalable production and rapid design possible even in modest facilities, researchers expect the impact of this technology to only grow through 2026 and beyond. Ashley Song (ashley@koreabizwire.
com).
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