Phage Therapy

Gladstone has received an initial $2 million award from the National Institute of Allergy and Infectious Diseases (NIAID), with the potential for up to $10 million over five years, to establish the Center for PhAIge Therapy. The center brings together researchers to develop engineered phage treatments for antibiotic-resistant bacterial infections and accelerate their path toward clinical use through iteration between phage genetics and AI modeling.

One major challenge in phage therapy is that naturally occurring phages have not necessarily evolved to kill the bacteria causing a patient’s infection. In Seth Shipman’s lab, scientists have developed technologies that allow them to rapidly edit phage genomes and to identify engineered phages that can kill infectious bacteria. This approach could make phage therapies more reliable, easier to customize, and scalable enough for broader clinical use.

Researchers are also studying the ongoing evolutionary battle between bacteria and phages. In the Silas lab, scientists are performing large-scale screens of tens of thousands of phage genes in wild bacterial strains to identify the genetic tools phages use to overcome bacterial defenses. These discoveries could help scientists engineer new phages capable of targeting some of today’s most dangerous antibiotic-resistant pathogens.

The Silas and Shipman labs share a focus on Klebsiella pneumoniae, a pathogenic bacteria at the origin of many hospital-acquired infections. Klebsiella forms a thick biofilm that protects it from the immune system and allows it to stick to medical equipment, making it difficult to clear. Moreover, it can readily acquire and share genetic material with other bacteria, including antibiotic resistance genes. By teasing apart the genetic interactions between various phages and various strains of Klebsiella, the labs aim to quicken the discovery of phage therapies against Klebsiella.