使用基因工程微生物治疗药物对人类肠道进行控制的殖民
Weston R Whitaker1,2, Zachary N Russ1, Elizabeth Stanley Shepherd1
1Novome Biotechnologies, South San Francisco, CA, USA.
Science (New York, N.Y.)
|July 17, 2025
概括
工程细菌可以逆向殖民肠道, 提供一种新的方法来治疗像高氧化症这样的疾病. 这种精确的微生物组编程在临床前模型和早期人体试验中显示出前景.
科学领域:
- 微生物组研究
- 合成生物学
- 胃肠病学
背景情况:
- 可复制结肠殖民是治疗微生物组应用的一个主要障碍.
- 之前的工作确立了在小鼠中使用波菲兰益生菌植入工程细菌的利基.
研究的目的:
- 设计一种可逆殖民结肠菌株.
- 通过将氧酸盐降解途径纳入工程菌株来开发超氧的治疗候选物.
主要方法:
- 在*P. vulgatus*中使用可逆植入的波菲兰诱导促进剂进行工程条件减弱.
- 将五个基因的氧酸盐降解途径纳入工程菌株中.
- 进行了临床前研究和1/ 2a期临床试验.
主要成果:
- 在人类中以剂量依赖的方式实现可逆植入*P. vulgatus*.
- 已证实尿液中氧酸盐水平的降低,表明对高氧化尿的有效性.
- 确定影响长期疗效的遗传稳定性挑战.
结论:
- 工程细菌的条件减弱和可逆植入对于治疗微生物组应用是可行的.
- 这种可降解氧酸盐的菌株具有治疗高氧的潜力.
- 需要进一步优化以解决持续治疗效益的遗传稳定性.
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