可编程的时代遗传基因电路用于自调节的生物药物的昼夜递送
Amanda Cimino1, Fiona Pat2, Omolabake Oyebamiji2
1Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children - Saint Louis, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University, St. Louis, MO 63105, USA.
概括
科学家们设计了具有昼夜基因电路的细胞,以产生类风湿性关节炎 (RA) 的互白素-1受体对手 (IL-1Ra). 这种自我调节的药物输送与身体的自然节奏保持一致,提供了一种新的慢性治疗方法.
科学领域:
- 生物技术是生物技术.
- 时间生物学 时间生物学
- 免疫学 免疫学 免疫学
背景情况:
- 身体的昼夜时钟调节日常生理过程,影响健康和诸如类风湿性关节炎 (RA) 这样的疾病.
- RA 涉及早晨的炎症性细胞因子峰值和关节硬,强调需要及时治疗.
- 目前对RA的慢性疗法,特别是基于细胞的疗法,还不发达.
研究的目的:
- 开发自主时代遗传基因电路,用于昼夜生产互白素-1受体对抗剂 (IL-1Ra).
- 为了比较这些电路中不同昼夜促进元件的疗效.
- 评估这些工程细胞在RA环境中的治疗潜力.
主要方法:
- 设计了自主时代遗传基因电路,以控制相位和振幅产生IL-1Ra.
- 在电路中利用了不同的昼夜促进元件 (E'-box,D-box,RRE).
- 在炎症条件下,在小鼠诱导的多能干细胞和软骨颗粒中测试电路功能和IL-1Ra的产生.
主要成果:
- 每个工程基因电路都表现出可靠的昼夜控制IL-1Ra表达,在不同的时间达到峰值.
- 工程细胞以昼夜方式产生大量的IL-1Ra.
- 由工程细胞产生的IL-1Ra赋予了对昼夜调节失调和炎症损伤的保护.
结论:
- 可以开发可编程的时代遗传电路,用于昼夜药物生产.
- 这些电路使得自我调节,定时的交付生物药物,如IL-1Ra.
- 这种方法有可能通过与个人昼夜节律保持一致来优化RA治疗.
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