Virginia Tech Scientists Engineer Gut Viruses to Act as Tiny Drug Factories

In a groundbreaking development, researchers at Virginia Tech have engineered viruses known as bacteriophages—or phages—to transform gut bacteria into miniature drug-producing units. This innovation, led by Dr. Bryan Hsu, assistant professor of biological sciences, in collaboration with Professor Liwu Li, addresses a long-standing challenge in drug delivery: surviving the harsh acidic conditions of the upper gastrointestinal (GI) tract.

Oral medications are highly desirable due to their noninvasive nature, but biologic drugs often struggle to reach the lower GI tract intact. The stomach's acidity breaks down these compounds before they can be absorbed where they're needed. To bypass this barrier, Hsu’s team harnessed phages—viruses that naturally infect bacteria—to deliver therapeutic proteins directly within the gut.

“By using bacteriophages, we can essentially reprogram bacteria to produce beneficial proteins,” Hsu explained. “It’s like turning them into tiny pharmacists.”

Phages resemble alien-like structures that inject genetic material into bacteria, prompting them to produce more phages. This self-replicating mechanism inspired the team to use phages as a delivery system for sustained drug production in the intestines. Notably, the human gut contains ten times more phages than bacteria, making them a promising tool for targeted treatment.

The team modified a specific phage known as T4, which targets common, non-pathogenic Escherichia coli found in the gut. They engineered T4 to produce a fluorescent protein called superfolder green fluorescent protein (sfGFP). When administered to mice, the fluorescent signals were clearly detected along the intestinal walls—right where protein absorption occurs.

Building on this success, the researchers conducted two proof-of-concept studies. In one, T4 was programmed to produce serine protease inhibitor (serpin), a protein known to combat ulcerative colitis, a type of inflammatory bowel disease. The treatment reduced symptoms in mice. In another experiment, the phage delivered ClpB, a protein that mimics satiety signals. Mice treated with this version of T4 showed decreased food intake and weight loss.

One remarkable finding was the phages’ ability to persist in the gut for weeks, enabling ongoing production of therapeutic proteins. This could open new avenues for delivering drugs that are otherwise difficult to administer orally.

However, challenges remain. Ensuring that these proteins are selectively absorbed by the body is not straightforward. The team likened this difficulty to issues seen with probiotics, which often fail to survive the stomach and establish themselves in the gut due to overcrowding by existing microbes.

“Achieving selective and efficient absorption is still a major hurdle,” Hsu noted. Yet, the self-replicating nature of phages offers a promising workaround.

As clinical trials loom on the horizon—typically a lengthy and complex process—Hsu’s team is also exploring the formation of a startup to commercialize this technology. Their ultimate goal is to offer a one-time dose of engineered phages that could address a range of gut-related health conditions.

Source:https://www.bio-itworld.com/news/2025/04/08/researchers-transform-gut-bacteria-into-little-pharmacists

This is non-financial/medical advice and made using AI so could be wrong.