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.<\/p>\n
In cultured Caco-2 and RAW264.7 cells, the system reduced NOX2 expression and ROS, while increasing antioxidant signalling through NRF2\u2013HO-1 and NRF2\u2013GPX4. 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.<\/p>\n
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.<\/p>\n