为siRNA输送设计的蛋白质的合理工程
Thomas G W Edwardson1, Takahiro Mori1, Donald Hilvert1
1Laboratory of Organic Chemistry , ETH Zurich , 8093 Zurich , Switzerland.
Journal of the American Chemical Society
|August 10, 2018
概括
研究人员开发了一种用于输送核酸疗法的新型蛋白. 这种工程囊有效地将小干扰RNA (siRNA) 输入细胞,使基因沉默和进步的寡核酸疗法成为可能.
科学领域:
- 生物技术
- 分子医学
- 药物输送系统
背景情况:
- 寡核酸治疗具有显著的医疗前景,但需要有效的输送系统.
- 目前的输送方法在有效地将核酸输送到目标细胞中面临挑战.
- 蛋白质是创造新型药物输送工具的潜在支架.
研究的目的:
- 将一个多孔的蛋白质变成一个功能性的核酸输送载体.
- 证明修改后的蛋白质能够封装和输送寡核酸.
- 通过哺乳动物细胞的RNA干扰 (RNAi) 验证该系统的治疗潜力.
主要方法:
- 设计了一个有孔的蛋白质, 在它的光表面有氨酸突变,
- 在体外工程蛋白质内封装的小干扰RNA (siRNA).
- 在哺乳动物细胞中评估siRNA载的细胞吸收.
- 通过RNA干扰评估了siRNA载荷的释放和随后的基因淘汰.
主要成果:
- 修改后的蛋白质有效地封装了具有高结合亲和力的寡核酸.
- 充满siRNA的子被哺乳动物细胞有效吸收.
- 成功释放siRNA货物导致RNA干扰和基因表达倒闭.
- 设计的蛋白质作为可行的核酸输送系统.
结论:
- 开发了一种简单的方法,将蛋白质转化为核酸输送载体.
- 积极超电的蛋白质促进了高效的寡核酸封装和细胞输送.
- 这种方法有望推进基于RNAi的治疗方法和其他核酸输送应用.
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