Published on 24/08/2026 – 7:02 GMT+2
Researchers at Johns Hopkins Medicine have discovered a potential method to increase protein output from mRNA therapies, a development that could enhance vaccines and treatments for cancer, infectious diseases, and autoimmune disorders.
The study, appearing in Nature, examines a naturally occurring RNA modification known as N4‑acetylcytidine (ac4C). Current mRNA platforms primarily rely on N1‑methylpseudouridine (m1Ψ), the modification used in the COVID‑19 vaccines and now being investigated for other therapeutic uses.
The investigators compared the two modifications in cultured human dendritic cells and mouse liver cells.
“Our findings show that ac4C leads to higher production of therapeutic proteins than the standard m1Ψ‑based platform,” said Bin Wu, associate professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine. “This could eventually yield more effective drugs that require lower doses.”
Although more than 170 RNA modifications exist, only a few have been explored for mRNA therapeutics. Wu notes that ac4C may improve mRNA translation, potentially accelerating protein synthesis.
Inside cells, ribosomes travel along mRNA strands, reading the genetic code and assembling proteins. The Johns Hopkins team observed that ribosomes moving along ac4C‑modified mRNA moved almost twice as fast as those on m1Ψ‑modified mRNA.
The researchers liken the effect to alleviating a traffic jam. “Our imaging revealed that ribosomes travel nearly twice as fast on the ac4C‑modified mRNA, preventing the ribosomal congestion we might see with the current mRNA platform,” Wu explained.
If validated in further studies, this insight could have major implications for the mRNA field. A key advantage of mRNA technology is its ability to instruct cells to temporarily produce a specific protein, but the quantity of protein generated often determines therapeutic success.
By enabling cells to produce more protein from the same amount of mRNA, future treatments might achieve their desired effects with smaller doses. This could benefit a widening pipeline of mRNA‑based vaccines against infectious diseases and experimental therapies aimed at stimulating anti‑tumor immunity or modulating immune responses in autoimmune conditions.
At present, ac4C remains experimental.
Nevertheless, if the ribosomal “traffic jam” identified by the team proves to be a meaningful limitation of existing mRNA platforms—and if ac4C can overcome it safely in living organisms—the discovery could become a significant step toward the next generation of mRNA medicines.
