RNA switch lets drugs control gene therapy protein production
Bioengineers at the University of California San Diego have developed a technology that allows drugs to control when cells produce therapeutic proteins, which could potentially make gene therapies safer and more adaptable for treating chronic diseases.
Bioengineers at the University of California San Diego have developed a groundbreaking technology that allows drugs to control the production of therapeutic proteins in cells, potentially making gene therapies safer and more adaptable for treating chronic diseases. This innovation could address the longstanding challenge in gene therapy of providing long-lasting treatment while preventing therapeutic proteins from reaching harmful levels of activity.
In preclinical studies, researchers utilized adaptamers—short RNA sequences that utilize small-molecule drugs to regulate protein production—to activate the generation of a protein called FGF21. This protein aids in regulating metabolism and has shown promise in treating obesity. However, excessive or prolonged exposure to FGF21 can lead to muscle loss and reduced bone density.
The adaptamer system, developed by researchers in the lab of Prashant Mali, a professor at UC San Diego's Jacobs School of Engineering, allows for the activation and subsequent reduction of protein production through drug dosing.
Drug exposure and concentration influence the strength of the adaptamer's activation, and removing the drug allows protein production to decline. This means that clinicians could potentially adjust treatment as a patient's needs change, increasing the drug dose to achieve the desired therapeutic effect and then reducing the dose or stopping the drug if protein levels become too high or side effects emerge.
Preliminary studies demonstrated that activating FGF21 production using a small-molecule drug resulted in significant weight loss, improved blood sugar regulation, and nearly eliminated fat buildup in the liver.
While the potential of this technology is promising, further research is needed to refine the system for use in brain gene therapies that require on-and-off activation and to develop safer methods for delivering molecules that promote tissue repair. The study's first author, bioengineering Ph.D. student Jack Bryant, emphasized the possible benefits of this drug-controlled gene therapy, which could provide clinicians with a way to fine-tune treatment as a patient's requirements evolve.
Written by urgent.news from Medical Xpress's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
