开发高亲和度结合人类血清白蛋白的DNA纳米结构
Aurélie Lacroix1, Thomas G W Edwardson1, Mark A Hancock2
1Department of Chemistry and Centre for Self-Assembled Chemical Structures (CSACS), McGill University , 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
Journal of the American Chemical Society
|May 6, 2017
概括
研究人员用树突性链设计了DNA结构,以结合人体血清白蛋白 (HSA). 这种策略增强了核酸的治疗稳定性和输送,显著增加了血清半衰期和维持细胞活性.
科学领域:
- 生物技术
- 纳米医学
- 提供药物
背景情况:
- 核酸疗法在稳定性和体内输送方面面临挑战.
- 人类血清白蛋白 (HSA) 含量丰富,半衰期长,有助于分娩.
- 它的特性使其成为适合药物和纳米颗粒的载体.
研究的目的:
- 开发一种对HSA具有高度亲和力的DNA结构的工程策略.
- 改善核酸治疗药物的稳定性和输送.
- 通过改变配体呈现来研究DNA-HSA相互作用的调节.
主要方法:
- 将树突链与DNA结合起来,形成DNA-HSA两.
- 使用解离常数 (Kd) 进行结合亲和度的表征.
- 对细胞活动和DNA结构的血清降解率的评估.
- 用两性联体对DNA纳米立方体进行特定位点的修饰.
主要成果:
- 经过工程设计的DNA两体显示出高亲和度与HSA (低纳米Kd) 的结合.
- HSA复杂化维持了寡核酸沉默的活性,并减缓了血清中的DNA降解.
- DNA-HSA复合物的血清半衰期达到了22小时,而非结合DNA的半衰期为几分钟.
- 在DNA纳米立方体上对连接体数量和方向的调节改变了HSA结合亲和力.
结论:
- 蛋白质特定的结合域可以合理地控制DNA纳米结构与生物系统的相互作用.
- DNA-HSA复合体为研究蛋白质吸附层提供了一种新的方法.
- 这一策略对RNAi疗法在体外和体外的有效输送具有重要意义.
相关概念视频
01:16The DNA Helix
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Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...