Engineered Phages Offer New Route for Gut-Specific Drug Delivery

A new study in Nature Biotechnology details an innovative method for delivering protein-based drugs directly to the lower gastrointestinal tract, bypassing the challenges of traditional oral medication. Biologist Bryan Hsu and his team from Virginia Tech, engineered bacteriophages—viruses that naturally infect bacteria—to reprogram gut bacteria into microscopic drug factories.

The team engineered phages to inject bacterial cells with genetic instructions. These instructions prompt the bacteria to produce therapeutic proteins in addition to creating more phages. As the bacteria rupture and release a flood of new phages, they also release a steady supply of the targeted protein inside the lower intestine.

The researchers demonstrated the potential of this technique by tackling symptoms associated with two separate diseases in mice. They successfully reduced inflammation by releasing a protein that inhibited an enzyme linked to inflammatory bowel disease, and they reduced obesity by releasing a protein that induced a feeling of fullness in mice given a high-fat diet.

These results demonstrate the potential for this novel approach to drug delivery. Hsu likens their progress to that of a delivery service: "It's like we're Amazon. We got the stuff there, we dropped it off on the doorstep. Now we need to figure out how to ring the doorbell."

The team is currently exploring the commercial applications of this innovation. Their next step involves developing methods to facilitate the absorption of these drugs from the gut into the bloodstream. The approach utilizes the natural abundance of phages within the gut microbiome, suggesting a new path for targeted therapies in the lower intestines.