在哺乳动物的肠道中,由工程化菌体维持在位蛋白质的生产和释放
Zachary R Baker1,2,3, Yao Zhang1, Haiyan Zhang4
1Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
Nature biotechnology
|February 18, 2025
概括
工程化菌体 (菌体) 通过感染肠道细菌来提供治疗性蛋白质,提供了一种新的口服生物药物递送系统. 这种方法可以减少结肠炎和肥胖模型中的炎症.
科学领域:
- 微生物学 微生物学
- 基因工程是一种基因工程.
- 胃肠病学 胃肠病学
背景情况:
- 口服生物药物递送面临由于胃肠道退化而面临的挑战.
- 用于肠道生物制剂的工程微生物受到居民细菌竞争的阻碍.
研究的目的:
- 为了设计菌体 (菌体),在哺乳动物肠道内表达治疗性蛋白质.
- 利用毒性菌体作为载体,从居住的共生细菌传递生物物质.
主要方法:
- 改造了毒性T4菌体以感染非致病性大肠杆菌.
- 确定了T4特异性促进剂,用于最大限度地表达蛋白质,对菌体标位的影响最小.
- 在工程T4菌体中表达了一种血清蛋白酶抑制剂.
主要成果:
- 在大肠炎的小鼠模型中,已证明减少了亲炎性酶活性.
- 在饮食诱导的肥胖小鼠模型中显示了减轻体重增加和炎症.
- 通过菌体诱导的细菌溶解验证了治疗性蛋白质释放.
结论:
- 病毒性菌体可以被设计为治疗性蛋白质在肠道中的有效载体.
- 这一战略克服了基于微生物的传递系统的局限性.
- 菌体介导蛋白质表达为治疗胃肠道疾病和代谢障碍提供了一个有前途的途径.
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