A team of researchers led by Dr. Kim V. Narry, Director of the Center for RNA Research at the Institute for Basic Science, has uncovered a crucial cellular mechanism that impacts the function of mRNA vaccines and therapeutics. Their study, published in Science, offers the first comprehensive understanding of how mRNA vaccines are delivered, processed, and degraded inside cells, which could lead to more effective RNA-based treatments.

Using CRISPR-based screening, the team identified three key factors involved in mRNA delivery. First, they found that heparan sulfate (HSPG) on the cell surface helps mRNA entry by attracting lipid nanoparticles (LNPs). Second, V-ATPase, a proton pump, enables LNPs to disrupt the endosomal membrane and release mRNA into the cytoplasm. Lastly, they discovered that TRIM25, a protein in the cellular defense system, rapidly degrades foreign mRNA. However, mRNA vaccines evade this defense through a modification called N1-methylpseudouridine (m1Ψ), which prevents TRIM25 from binding to mRNA, improving the stability and effectiveness of the vaccines.

The study also revealed the role of proton ions in activating TRIM25, marking the first demonstration that proton ions act as immune signaling molecules. Dr. Narry emphasized that understanding how cells respond to mRNA is essential for improving RNA therapeutics. This research not only enhances mRNA vaccine delivery but also provides new avenues for developing RNA-based treatments for various diseases.

Source: https://www.ibs.re.kr/cop/bbs/BBSMSTR_000000000738/selectBoardArticle.do?nttId=25755&pageIndex=1&searchCnd=&searchWrd=