by Lasha Markham, Texas A&M University, edited by Stephanie Baum, reviewed by Robert Egan. Credit: CC0 Public Domain
What if a cup of coffee could help treat cancer? Researchers at the Texas A&M Health Institute of Biosciences and Technology believe it’s possible. By combining caffeine with the use of CRISPR—a gene-editing tool known as clustered regularly interspaced short palindromic repeats—scientists are unlocking new treatments for long-term diseases, like cancer and diabetes, using a strategy known as chemogenetics.
The work is published in the journal Chemical Science.
Yubin Zhou, professor and director of the Center for Translational Cancer Research at the Institute of Biosciences and Technology, specializes in utilizing groundbreaking tools and technology to study medicine at the cellular, epigenetic and genetic levels. Throughout his career and over 180 publications, he has sought answers to medical questions by using highly advanced tools like CRISPR and chemogenetic control systems.
Chemogenetics refers to the ability to control cellular behavior using externally applied, small molecules—often drugs or dietary compounds—that activate genetically engineered switches inside cells. Unlike traditional drugs that broadly affect many tissues, chemogenetic approaches are designed to act only on cells that have been genetically programmed to respond.
Gene editing with a kick
Zhou’s newest research builds on existing knowledge of genetic “switches” within cells by introducing a new chemogenetic approach that uses CRISPR and caffeine. The process begins with installing the cells in advance. Genes encoding the nanobody, its matching target protein and the CRISPR machinery are delivered using established gene-transfer methods, allowing cells to produce these components on their own.
Once this molecular framework is in place, the process can be externally controlled. When a person later consumes a 20 mg dose of caffeine—such as from coffee, chocolate or a soda—it triggers a nanobody and its matching target protein to bind together, thereby activating CRISPR-driven gene modifications inside cells.
This method also allows scientists to activate T cells, something not possible with other gene-editing methods. T cells serve as the body’s memory bank for past infections, storing blueprints that help fight future threats. Being able to manually activate these cells could give researchers a new way to direct the immune system against specific diseases.
In addition, the team found that certain drugs can reverse the process by causing the proteins to separate, stopping further gene changes and offering even more control over how the system is used, an important feature for safe and reversible chemogenetic therapies. For example, in a therapeutic setting, clinicians could temporarily pause gene-modifying activity to give patients a break from treatment-related stress or side effects, then re-activate the system when conditions are optimal—allowing gene control to be tuned over time rather than left permanently switched on.
“You can also engineer these antibody-like molecules to work with rapamycin-inducible systems, so by adding a different drug like rapamycin, you can achieve the opposite effect,” Zhou said. “For example, if at first proteins A and B are separate, adding caffeine brings them together; conversely, if proteins A and B start out together, adding a drug like rapamycin can cause them to dissociate.”
Rapamycin is a widely available immunosuppressant drug traditionally used as an anti-rejection regimen for organ transplant patients. The drug works by blocking white blood cells from attacking foreign entities in the body. The affordability and availability of the drug make it a prime candidate for applications like this one.
