{"id":"doi:10.1002/advs.202520434","kind":"article","title":"Dual-Key Genetic Circuit Enables Stable and Self-Regulated Engineered Bacteria for the Treatment of Ulcerative Colitis","authors":["Ding S","Yang B","Li X","Wang Y","Huang C","Dong W","Xie W"],"author_count":7,"year":2026,"published":"2026-02-13","venue":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","cited_by":1,"doi":"10.1002/advs.202520434","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/advs.202520434","archive_url":"https://space-kitty.com/papers/doi:10.1002/advs.202520434","updated":null,"pmid":"41685627","pmcid":"PMC13104102","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13104102/pdf","abstract":"Engineered bacteria offer a promising therapeutic platform but often display plasmid instability and antibiotic dependence. A synthetic dual-key genetic circuit is established in Escherichia coli Nissle 1917 (EcN) by deleting both asd and thyA genes, generating an auxotrophic chassis that requires dual-plasmid complementation for survival. The \"lysis module\" restores asd function and incorporates a quorum-sensing system for self-regulated lysis and controlled protein release (\"One Key\"). By contrast, the \"expression module\" complements thyA and co-delivers an interleukin-2 (IL-2) mutant and the membrane protein Amuc_1100 to modulate immune balance and repair the intestinal barrier (\"Dual Keys\"). This dual-key design enabled antibiotic-free plasmid stability, precise population control, and sustained therapeutic protein secretion. Oral administration of the engineered strain significantly alleviated colitis in mice by enhancing regulatory T-cell expansion, restoring epithelial integrity, and reshaping the gut microbiota. This modular system provides a safe, stable, and programmable strategy for live bacterial therapy against immune and mucosal diseases.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Dual-Key Genetic Circuit Enables Stable and Self-Regulated Engineered Bacteria for the Treatment of Ulcerative Colitis\" by Ding S, Yang B, Li X et al., https://doi.org/10.1002/advs.202520434, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"synthetic-biology","name":"Synthetic Biology & Genome Engineering","domain_slug":"biotech"}],"cited_in_dossiers":[]}