级联动态组装/拆卸DNA纳米框架,使得CRISPR-Cas9系统的可控传递
Nachuan Song1, Yiwen Chu1, Shuai Li1
1Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), Institute of Biomolecular and Biomedical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, P.R. China.
Science advances
|August 30, 2023
概括
研究人员开发了一种动态DNA纳米框架,用于控制CRISPR-Cas9 (基因编辑工具) 核糖蛋白 (RNP) 到癌细胞的输送. 该系统显示高基因编辑效率和抗瘤疗效,毒性低.
科学领域:
- 生物技术是生物技术.
- 纳米技术纳米技术
- 分子生物学分子生物学
背景情况:
- 克里斯普尔-Cas9基因编辑对降低调节标基因具有治疗潜力.
- Cas9核核蛋白 (RNP) 综合体的有效输送对于治疗成功至关重要,但仍然是一个重大挑战.
- 开发先进的传递系统对于充分利用CRISPR-Cas9疗法的全部潜力至关重要.
研究的目的:
- 设计一种能够控制Cas9 RNP传递的新型DNA纳米框架 (NF).
- 为了实现NF的动态组装和拆卸,以有针对性的释放Cas9 RNP.
- 评估Cas9 RNP装载NF系统的治疗疗效和安全性.
主要方法:
- 使用烯胺修饰的DNA和级联杂交连锁反应 (HCR) 制造DNANF,用于单导向RNA结合和Cas9蛋白加载.
- 设计具有响应元素的NF (水友性/疏水性组,二硫化键) 以实现动态膨胀,聚合和触发拆卸.
- 在乳腺癌小鼠模型中,对基因编辑效率,细胞毒性和抗瘤活性进行了NF系统的体外和体内测试.
主要成果:
- DNA NF成功地结合了单导向RNA和加载的Cas9蛋白,从而实现了受控的RNP传递.
- 该NF表现出动态的胀和聚合,随着针对癌细胞特异性谷氨的反应引发了分解.
- 在癌细胞中观察到高基因编辑效率,正常细胞中最小的毒性和显著的抗瘤疗效.
结论:
- 开发的级联动态组装/拆卸DNA纳米框架为控制的Cas9 RNP交付提供了一个有效的平台.
- 该系统为针对性基因编辑疗法提供了一个有希望的策略,其安全性和有效性得到了提高.
- 这些发现突出了响应性纳米结构在推进基于CRISPR的治疗应用中的潜力.
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