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双键基因电路使得稳定和自我调节的工程细菌能够用于治疗性结肠炎
Shuaijie Ding1, Biao Yang1, Xinyu Li1
1Institute of Health and Medicine (IHM), Hefei Comprehensive National Science Center, Hefei, Anhui, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 13, 2026
概括
带有合成双键电路的工程细菌实现了稳定,无抗生素的等离子体维护. 这种活体细菌疗法通过控制蛋白质释放和调节免疫反应,有效治疗小鼠结肠炎.
科学领域:
- 合成生物学 合成生物学
- 微生物治疗学 微生物治疗学
- 免疫学 免疫学 免疫学
背景情况:
- 工程细菌显示出治疗潜力,但面临着等离子体不稳定性和抗生素依赖性的挑战.
- 开发稳定可控的细菌底盘对于有效的活细菌疗法至关重要.
- 目前的策略通常需要抗生素,限制其安全性和适用性.
研究的目的:
- 在Escherichia coli Nissle 1917 (EcN) 中设计合成双键遗传电路,以提高稳定性和控制蛋白质的输送.
- 建立一个无抗生素的活体细菌疗法系统.
- 在大肠炎的小鼠模型中评估工程EcN菌株的治疗疗效.
主要方法:
- 在EcN中删除asd和thyA基因以创建需要双等离子体补充的辅助性底盘.
- 构建一个"溶解模块",配备定数感应系统,用于调节细胞溶解和蛋白质释放.
- 开发一种"表达模块"来补充thyA并提供治疗性蛋白质 (突变IL-2和Amuc_1100).
主要成果:
- 双键基因电路确保了无抗生素等离子体的稳定性和精确的人口控制.
- 工程 EcN 证明了治疗性蛋白质的持续分泌.
- 口服工程 EcN 显著缓解小鼠结肠炎,促进调节性 T 细胞扩张,恢复上皮质完整性,并重塑肠道微生物群.
结论:
- 合成双键系统提供了一个安全,稳定和可编程的平台,用于活细菌治疗.
- 这种方法克服了塑体不稳定性和工程细菌对抗生素依赖性的局限性.
- 工程 EcN 菌株在治疗免疫和粘膜疾病,如结肠炎方面表现有前途.
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