Revolutionizing Drug Delivery: Gut Bacteria Turned into Microscopic Pharmacies

Virginia Tech researchers have made a groundbreaking discovery in gastrointestinal drug delivery by transforming gut bacteria into microscopic protein factories. This innovation enables continuous and precise protein-based therapies directly in the lower intestine, offering new hope for chronic diseases such as inflammation and obesity.

Hundreds of Microbial Species in Your Gut

Your gut is teeming with hundreds of different microbial species. In the future, one of these could play a crucial role as an in-house pharmacist, producing targeted therapies from within your body.

Engineering Gut Bacteria

A study published on February 18th in Nature Biotechnology showcased a method to program gut bacteria to produce and release proteins within the lower gastrointestinal tract, overcoming a significant challenge in drug delivery to this region.

The Barrier of Oral Medications

Oral medications are common and practical, but the stomach’s acidic environment breaks down most substances before they can reach the intestines. This barrier is beneficial for clearing foodborne pathogens but poses a problem for drugs intended to treat conditions in the gut, which often get deactivated and expelled.

The Solution: Engineered Bacteriophages

Bryant Hsu’s team engineered bacteriophages—viruses that naturally infect bacteria—to reprogram bacterial cells to produce and release a sustained flow of protein-based drugs. Collaborating with immunologist Liwu Li, Hsu’s team demonstrated the potential of this approach for chronic disease treatments.

Understanding Bacteriophages

Bacteriophages, or phages, are viruses that infect bacteria. They inject their DNA into bacterial cells, redirecting them to produce more phages, leading to bacterial cell destruction and the release of new phages. This process can be harnessed to produce therapeutic proteins directly within the gut.

Injecting Genetic Information

Zachary Baker, a doctoral student in the Hsu Lab, engineered phages to introduce additional genetic material into bacterial cells. This instructed the cells not only to produce new phages but also to create a therapeutic protein that could be used in targeted therapies within the lower intestine.

Successful Trials in Mice

To test their method, Baker and Yao Zhang applied the engineered phages to mice with conditions associated with two separate diseases:

• Inflammation: By releasing a protein that inhibits an enzyme linked to inflammatory bowel disease.
• Obesity: By releasing a protein that stimulates a feeling of satiety in mice given a high-fat diet, mirroring the effects of a typical Western diet.

These trials in mice demonstrated the potential of phage-based protein delivery for chronic diseases.

Commercial Potential and Future Directions

Hsu’s team is currently exploring the commercial potential of this innovation through the National Science Foundation I-Corps program and the Fralin Commercialization Fellowship. However, the researchers acknowledge that delivering drugs from the gut into the systemic circulation remains a significant challenge.

“It’s like we’re Amazon. We got the stuff there, we dropped it off on the doorstep,” Hsu said. “Now we need to figure out how to ring the doorbell.”

Next Steps

Funding for this groundbreaking research has come from the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, and the Lay Nam Chang Dean’s Discovery Fund, awarded by the Virginia Tech College of Science.

This discovery opens new avenues for targeted drug delivery, potentially transforming treatments for chronic gastrointestinal conditions. As research progresses, the benefits of this innovation could extend to millions of people worldwide.

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