Researchers at Texas A&M Health report that pairing caffeine with CRISPR gene editing allows precise, reversible control of genes in engineered cells, a chemogenetic approach known as Caffeine Triggered Gene Editing that could advance treatments for cancer, diabetes, and immune disorders.
Researchers at the Texas A&M Health Institute of Biosciences and Technology say a common stimulant found in coffee, tea, and chocolate may help scientists control when and how genes are edited inside human cells.
The team has combined caffeine with CRISPR, the gene-editing technology formally known as clustered regularly interspaced short palindromic repeats, to create a system that turns gene modifications on and off using small, familiar molecules. The strategy relies on chemogenetics, which uses external compounds to activate genetically programmed switches inside cells.
“This approach allows us to control powerful gene-editing tools with simple, well-understood molecules,” said Yubin Zhou, a professor and director of the Center for Translational Cancer Research at the institute.
Caffeine Acts as a Molecular Switch
Zhou’s group developed a system in which cells are first engineered to produce several components, including CRISPR machinery and a pair of proteins designed to respond to caffeine. These components are delivered using established gene-transfer techniques.
Once the system is installed, consuming about 20 milligrams of caffeine can trigger the proteins to bind together, activating CRISPR inside the cell and initiating targeted gene changes. That amount of caffeine can be found in small servings of coffee, soda, or chocolate.
The protein engineered to respond to caffeine is known as a “caffebody,” an antibody-like molecule designed to bind only when caffeine or its metabolites are present. According to Zhou, this design ensures that Caffeine triggered gene editing occurs only in cells programmed to respond.
“Unlike traditional drugs that affect many tissues at once, chemogenetic systems are selective,” Zhou said. “Only the engineered cells respond to the signal.”
New Control Over Immune Cells
One key advance is the ability to activate T cells, a critical part of the immune system that retains memory of past infections. Existing gene-editing approaches offer limited control over when these cells are activated.
By using caffeine-responsive switches, researchers can direct T cells to turn gene programs on for a few hours, roughly matching the time caffeine remains active in the body. This control could be valuable in cancer therapy, where precisely timed immune responses are essential.
In laboratory studies using animal models, the team also found that caffeine metabolites such as theobromine, commonly found in cocoa, could activate the same system. Zhou said this flexibility could make the technology easier to adapt in clinical settings.
“It gives us a window of control that we did not have before,” he said.
Reversible Editing Improves Safety
The system includes a built-in stop mechanism. Certain drugs, including rapamycin, can cause the interacting proteins to separate, halting further Caffeine triggered gene editing. Rapamycin is an immunosuppressant widely used in organ transplant patients and is already approved for medical use.
This start-and-stop capability allows clinicians to pause treatment if patients experience side effects, then resume gene activity later. Zhou said few existing gene-editing approaches offer this level of reversible control.
“You can tune the system over time instead of leaving it permanently on,” he said.
Looking ahead, Zhou believes the technology could be adapted to treat diabetes by allowing engineered cells to increase insulin production in response to Caffeine triggered gene editing. Similar strategies could be used to regulate immune attacks on tumors or control other therapeutic genes.
The team plans to advance the work into further preclinical studies and explore additional medical applications.
“Our goal is to repurpose familiar molecules as precise control signals for advanced therapies,” Zhou said. “That could make gene and cell treatments safer, more practical, and easier to translate into real-world medicine.”
