Probiotics: CRISPR-Engineered Probiotics Edit NOX2 in Mouse Colitis

The Chinese researchers equipped Escherichia coli Nissle 1917 with plasmids encoding Cas9 and a single-guide RNA targeting NOX2/gp91phox. The bacteria were encapsulated in a hyaluronic acid-chitosan-magnesium hydrogel, which increased survival after simulated gastrointestinal exposure from 0.07% to 12% and prolonged intestinal retention. Cas9 expression was controlled with IPTG.

In cultured Caco-2 and RAW264.7 cells, the system reduced NOX2 expression and ROS, while increasing antioxidant signalling through NRF2–HO-1 and NRF2–GPX4. In mice with dextran sodium sulphate-induced colitis, oral treatment produced more than 40% editing at the target site, reduced colonic NOX2 expression by approximately 40%, improved disease activity and partly restored crypt and epithelial-barrier integrity. Changes in proline and glutamate metabolism were associated with increased glutathione, while the gut microbiota shifted towards the composition of healthy controls.

The experiments involved only cells and groups of five mice. The authors note that broader safety testing and more sensitive analyses of possible off-target editing are required.

The study was led by Chen Zhang and Xiuli Bi at Liaoning University. It was published in Cell Reports Medicine on 24 July 2026.