Researchers at Texas A&M’s Health Science Center have developed a photo-inducible binary interaction tool, or PhoBIT, system — one made to regulate gene therapy, cell signaling and even cell death. The system acts as a light switch, allowing researchers to control cellular processes with extraordinary precision.
“We wanted a way to control biology with a tiny light switch,” PhoBIT researcher and co-author of the PhoBIT paper Dr. Tien-Hung Lan said. “Most existing tools are bulky and can interfere with normal protein function. By redesigning a natural tag-and-binder pair to respond to light, we created PhoBIT — a small, precise tool that lets scientists turn cellular pathways on or off with pinpoint accuracy.”
PhoBIT’s novel approach to gene and cellular regulation promises to revolutionize immunotherapy, regenerative medicine and cancer therapy.
Traditional cancer treatment relies on methods that, while effective, can cause a wide variety of harmful side effects. According to the National Cancer Institute, treatments such as chemotherapy, surgery and radiation therapy can cause neutropenia — a decrease in white blood cells — lymphedema —- painful swelling in a particular area of the body that raises the risk of infection — and blood clots — which can lead to life-threatening complications like pulmonary embolism.
“Most cancer therapies, like gene or immunotherapies, have high potential but come with serious side effects,” Lan said. “While they can effectively kill cancer cells, they can also interfere with the normal immune system. These adverse effects are a major concern because, in targeting the tumor, the treatments may unintentionally harm healthy cells or disrupt overall immune function.”
To address the fundamental limitations of existing tools and the critical need for precision in therapeutics, A&M’s team engineered the PhoBIT system.
PhoBIT innovates the way in which cancer can be treated by providing a safer and more precise option for treatment. It works by using blue light to guide an amino acid called sspB and allowing it to bind to ssrA, which manipulates gene and protein function. In turn, the sspB amino acid is able to react to light because of its fusion with a light domain.
The research team developed two different light-controlled switches, PhoBIT1 and PhoBIT2, which incorporate the LOV2 and CRY2 light domains respectively. In PhoBIT1, the LOV2 domain causes the ssrA-sspB complex to dissociate and cease protein interactions when exposed to blue light. The opposite occurs in PhoBIT2: when exposed to blue light, the sspB-CRY2 pair binds to ssrA and activates protein interactions.
“Because it only requires a seven-amino acid tag, PhoBIT is far less likely to disrupt natural protein function,” Lan said. “The same tag can be used to switch protein activity off or on with light, giving researchers flexible control over cellular processes. This reversible and precise system has been applied to diverse areas, from gene editing and immune signaling to cancer pathways, and has already shown therapeutic potential by shrinking tumors in animal models.”
PhoBIT’s simple yet advanced design allows it to precisely control protein interactions and cellular processes. In gene regulation, when blue light is dimmed, gene expression is halted; when light is turned on, gene expression resumes seamlessly, allowing scientists to make split second alternations to gene activity.
Furthermore, in cell signaling, PhoBIT is attached to a receptor that normally relies on hormonal signals, allowing cellular interaction to be modified instantly. As a result, PhoBIT enables scientists to study cellular processes more precisely and in real time, opening avenues for improved biological research.
“PhoBIT allows gene and protein therapies to be switched on only when needed, enabling safer, more controllable dosing,” Lan said. “Because the parts are small, they’re easier to package into standard delivery systems used in medicine.”
PhoBIT’s applications also extend to improved cancer therapy. The research team developed a synthetic protein that binds to BCR-ABL, a leukemia-driving protein, when exposed to light. This approach allows therapies to target specific areas affected by cancer, preventing healthy tissues from being damaged
“PhoBIT can confine anti-cancer activity to the tumor with a beam of light, helping protect healthy tissue,” Lan said. “In early mouse studies, this targeted control slowed tumor growth, pointing to a new layer of safety and precision.”
While PhoBIT has demonstrated precise control in the lab, the next step for the team is to translate these capabilities into therapies that can be effective for human patients. The team also aims to lay the groundwork for further related studies that could transform medical and biological research.
“We’re engineering versions that work with deeper-penetrating red, near-infrared light and pairing PhoBIT with clinically practical delivery methods,” Lan said. “Beyond cancer, we see opportunities in immune disorders, regenerative medicine and smart cell therapies, in partnership with clinicians.”