益生菌中的遗传密码扩展使小鼠能够分泌共价蛋白药物
Kaiyi Wang1, Yumeng Wu1, Jiamin Shang1
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
工程细菌现在可以使用遗传密码扩展产生新的治疗蛋白质. 这项突破使人能够口服定制的生物药物,
科学领域:
- 生物技术
- 合成生物学
- 微生物疗法
背景情况:
- 通过口服提供蛋白质疗法具有挑战性.
- 工程微生物提供局部肠道药物合成,但仅限于20种正规氨基酸,限制有效载荷的多样性.
研究的目的:
- 克服微生物治疗中的氨基酸限制.
- 通过基因代码扩展 (GCE) 建立一个多功能平台来生产增强的生物有效载荷.
主要方法:
- 设计了益生菌Escherichia coliNissle 1917 (EcN) 加入非正规的氨基酸硫酸-l-氨酸 (FSY).
- 实现了局部修饰的共价抗IL-23纳米体的分泌.
- 在小鼠结肠炎模型中口服工程EcN与FSY补充剂.
主要成果:
- 成功地将FSY纳入分泌的纳米体,达到皮科莫尔结合强度 (5.9 pM).
- 经过人工合成的EcN和FSY口服后,小鼠的结肠炎显著改善.
- 验证了该平台扩大活生物疗法的功能范围的能力.
结论:
- 在细菌治疗中集成的遗传密码扩展 (GCE) 克服了正规氨基酸的局限性.
- 工程 EcN 分泌改造的纳米体提供了一种新的口服治疗策略.
- 这种平台显著扩大了与肠道相关疾病的活生物疗法的治疗潜力.
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