Smart mRNA drugs listen to the body, adjusting protein production based on disease-related signals

A research team from The University of Osaka and the Institute of Science Tokyo has developed a class of mRNA medicines that can sense changes in the body and autonomously adjust their therapeutic effect. This innovation paves the way for precision treatments that are not only more effective, but also safer—by producing just the right amount of medicine based on real-time biological signals. The research is published in the journal NPG Asia Materials.

The new mRNA medicine works by responding to specific “humoral factors,” such as hormones or inflammation-related molecules, which signal the state of disease in the body. When these factors are present, the mRNA adjusts how much therapeutic protein is produced. This allows the medicine to adapt to changes in the body—just like a smart thermostat adjusts room temperature.

To achieve this, the team designed a system using three synthetic mRNAs:

1. An mRNA that produces a receptor protein to detect disease signals
2. An mRNA that makes a regulatory protein to control translation
3. A therapeutic mRNA that encodes the protein drug itself

These components work together like a logic circuit. When a target molecule like a hormone or inflammatory signal is detected, the system activates the therapeutic protein.

The team demonstrated that this system could respond to various disease-related molecules, such as arginine vasopressin (a hormone related to water balance), prostaglandin E₂ (a marker of inflammation), and bradykinin (linked to pain). In one experiment, the system was able to suppress inflammatory signals by producing anti-inflammatory proteins only when the inflammatory marker was detected.

Traditional drugs deliver a fixed dose, regardless of the patient’s condition at any given moment. Overdosing can lead to side effects, while underdosing may reduce effectiveness. This new self-regulating system offers a solution—a drug that tunes itself in real time to match what the body needs.

This technology could be particularly useful for conditions that change frequently, like chronic pain or inflammatory diseases. It could also be used to improve the safety and effectiveness of mRNA vaccines by adjusting immune responses as needed.

“This is a major step toward precision mRNA therapy,” said Hideyuki Nakanishi, one of the lead researchers. “One key feature of our system is that all components are made entirely of mRNA. By integrating sensing and response into the medicine itself, we can reduce side effects and optimize treatment—all without external control.”

More information:
Hideyuki Nakanishi et al, Extracellular ligand-responsive translational regulation of synthetic mRNAs using engineered receptors, NPG Asia Materials (2025). DOI: 10.1038/s41427-025-00607-6

Provided by
University of Osaka