Scientists have developed a new way to control how medicines work inside the body, potentially leading to safer and more precise treatments.
The breakthrough, reported in Nature, allows researchers to control not just whether a drug binds to its target, but also how long it stays bound—a factor that could be the key to making therapies safer.
Traditionally, medicines are controlled by dose: take more for a stronger effect, less for a weaker one. But this approach can be risky.
Many drugs, especially antibody therapies and immune-boosting treatments, can cause serious side effects once they begin working. Shutting them off quickly has not been possible—until now.
The research team, led by Professor David Baker at the University of Washington School of Medicine, designed custom proteins that could attach to specific targets in the body.
Then, using an added molecule called an effector, the scientists could force the protein-target pair into a strained shape, breaking them apart almost instantly.
“In one experiment, interactions that would normally last 20 minutes broke apart in just 10 seconds,” said lead author Adam Broerman, a Ph.D. student in chemical engineering.
“I had to repeat the tests multiple times before I could believe how fast it happened.”
The researchers tested their design on interleukin-2 (IL-2), a powerful immune protein that has been studied as a cancer therapy for years but is known for dangerous side effects.
They created a switchable version of IL-2 that could activate immune cells in the lab and then be turned off on demand with an effector. This level of control could allow doctors to give patients stronger, shorter treatments while avoiding life-threatening complications.
The team also demonstrated the potential of the switch in other applications, including diagnostics.
They engineered a light-emitting enzyme that could be toggled on and off within seconds, creating a bright, rapid signal.
By adapting the system, they built a coronavirus sensor that worked about 70 times faster than previous protein-based tests for SARS-CoV-2. The same approach could be used to design rapid sensors for other diseases, pollutants, or chemical markers.
This work represents a major leap in protein engineering, giving scientists a second “lever” to control drug activity in the body: not just dose, but duration.
If developed further, these protein switches could lead to a new generation of cancer therapies and diagnostics that are both more powerful and much safer for patients.
The project brought together expertise from several labs, including collaborators at Osnabrück University, Stanford University, and Oregon Health & Science University, who contributed critical measurements and simulations to test the designs.
By creating a way to turn protein-based drugs and sensors on and off almost instantly, the researchers have opened the door to medicines that work more like smart devices—responsive, precise, and safe.
