Researchers at Texas A&M University have developed a chemogenetic system that uses caffeine to activate CRISPR gene editing in cells, potentially aiding treatments for cancer and diabetes. The method allows precise control over gene modifications by consuming small amounts of caffeine from everyday sources like coffee or chocolate. This approach aims to enhance immune responses and insulin production with reversible activation.
Scientists at the Texas A&M Health Institute of Biosciences and Technology are exploring a novel way to integrate caffeine with CRISPR, the clustered regularly interspaced short palindromic repeats gene-editing tool. Led by Yubin Zhou, professor and director of the Center for Translational Cancer Research, the team has engineered a chemogenetic system that responds to chemical signals from common substances.
The process begins with preparing cells using gene transfer techniques to insert components: a nanobody, its target protein, and CRISPR machinery. Once inside the cell, these elements are produced naturally. Consuming approximately 20 mg of caffeine—found in coffee, chocolate, or soda—triggers the nanobody to bind with its partner protein, activating CRISPR for targeted gene edits. This method is particularly useful for programming T cells, the immune system's memory cells, to mount responses against diseases like cancer.
The system offers reversibility, as certain drugs can separate the proteins and halt editing. For instance, rapamycin, an immunosuppressant used in organ transplants, can induce dissociation. Zhou explained, "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."
Referred to as "caffebodies" when caffeine-responsive, these tools show promise beyond cancer. In diabetes management, they could enable insulin production boosts via coffee consumption. Laboratory studies on animals confirmed that caffeine and metabolites like theobromine from chocolate activate the response, providing a few hours of controlled editing before metabolization.
Zhou highlighted the system's modularity: "It's quite modular. You can integrate it into CRISPR and chimeric antigen receptor T (CAR-T) cells, and also if you want to induce some therapeutic gene expression like insulin or other things, and this is fully tunable in a very precisely controlled manner."
The researchers plan further preclinical testing to advance this toward clinical applications, emphasizing the use of familiar compounds for safe, adjustable therapies. Zhou noted, "What excites us is the idea of repurposing well-known drugs and even commonly found food ingredients like caffeine to do entirely new tricks."
This development builds on Zhou's extensive work, including over 180 publications on cellular and genetic disease mechanisms.
