A group of Penn scientists has developed a new method to remotely control engineered cells inside the human body using heat.
Led by bioengineer Lukasz Bugaj, the innovation introduces a temperature-sensitive protein called "Melt," which can be activated or deactivated by subtle temperature changes. This technology could revolutionize cancer treatment by precisely directing therapeutic cells to their targets.
“There’s a lot going on in complex living systems, so when we send modified cells into the body to execute a function — like finding pathogens or cancerous cells — wouldn’t it be great if we could communicate with them, guide them, and make sure they’re going exactly where they need to go, at the right time, to do the right thing?” Bugaj told Penn Today.
The idea builds on optogenetics, a field that uses light to control cellular activity. While effective in research, optogenetics is limited because light cannot penetrate deeply into human tissue. Bugaj's team initially studied Botrytis cinerea, a fungus that produces BcloV4, a light-sensitive protein. However, when introduced into cells, they noticed that it not only responded to light but also temperature.
They then modified BcLOV4 into a new protein that exclusively responded to temperature known as Melt — Membrane Localization using Temperature.
By fusing Melt to different cellular pathways, the researchers gained precise control over cell signaling, protein breakdown, and even programmed cell death. In one experiment, cooling a targeted area with a specialized ice pack triggered cancer cell death without the widespread toxicity of chemotherapy.
“We broke its light sensitivity and tuned its temperature sensitivity to operate at human body temperatures,” Pavan Iyengar, a former Penn undergraduate researcher in the Bugaj Lab, said. “Now we have a switch that works like a dimmer — you raise the temperature, and it activates; lower it, and it deactivates.”
Penn Medicine also advanced cancer treatments this year through CAR T-cell therapy, which reprograms immune cells to attack cancer, and by producing new nano-sized drug capsules that deliver targeted treatments.
Bugaj’s lab recently secured an NIH grant and funding from the Center for Precision Engineering for Health at Penn to further their research. In the future, the team hopes to develop cell therapies that naturally respond to bodily cues like fever or inflammation, creating more precise and adaptive treatments.
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