# Dual-Key Genetic Circuit Enables Stable and Self-Regulated Engineered Bacteria for the Treatment of Ulcerative Colitis

Article · Ding S, Yang B, Li X, Wang Y, Huang C, Dong W, Xie W

- Archive id: doi:10.1002/advs.202520434
- Published: 2026-02-13
- Venue: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
- DOI: https://doi.org/10.1002/advs.202520434
- PMID: 41685627
- PMCID: PMC13104102
- Citations: 1
- Source URL: https://doi.org/10.1002/advs.202520434
- PDF: https://europepmc.org/articles/PMC13104102/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Synthetic Biology & Genome Engineering](https://space-kitty.com/topics/synthetic-biology)

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