Department of Chemistry and Center for DNA Nanotechnology, Aarhus University, Aarhus, Denmark.
Nanomedicine. 2012 Jul;8(5):673-81. doi: 10.1016/j.nano.2011.08.011. Epub 2011 Sep 1.
Control over thrombin activity is much desired to regulate blood clotting in surgical and therapeutic situations. Thrombin-binding RNA and DNA aptamers have been used to inhibit thrombin activity and thus the coagulation cascade. Soluble DNA aptamers, as well as two different aptamers tethered by a flexible single-strand linker, have been shown to possess anticoagulant activity. Here, we link multiple aptamers at programmed positions on DNA nanostructures to optimize spacing and orientation of the aptamers and thereby to maximize anticoagulant activity in functional assays. By judicious engineering of the DNA nanostructures, we have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than free aptamer. Reversal of the thrombin inhibition was also achieved by the use of single-stranded DNA antidotes, thus enabling significant control over blood coagulation.
Thrombin inhibition via DNA aptamers has recently become a possibility. In this study, thrombin-binding DNA aptamers were further optimized by nanoscale organization on DNA nanostructures. The authors have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than that of free aptamer. Reversal of thrombin inhibition was also achieved by single-stranded DNA antidotes, enabling significant control over the coagulation pathway.
控制凝血酶活性对于控制手术和治疗过程中的血液凝结非常重要。凝血酶结合 RNA 和 DNA 适体已被用于抑制凝血酶活性和凝血级联反应。可溶性 DNA 适体以及通过柔性单链接头连接的两种不同适体已显示出抗凝活性。在这里，我们将多个适体连接到 DNA 纳米结构上的预定位置，以优化适体的空间排列和取向，从而在功能测定中最大限度地提高抗凝活性。通过对 DNA 纳米结构进行明智的工程设计，我们创建了一种新型的功能性 DNA 纳米结构，它是一种多适体抑制剂，其活性比游离适体高 8 倍。通过使用单链 DNA 解毒剂也可以逆转凝血酶抑制，从而能够对血液凝固进行显著控制。
通过 DNA 适体抑制凝血酶最近成为可能。在这项研究中，通过 DNA 纳米结构上的纳米级组织进一步优化了凝血酶结合 DNA 适体。作者创建了一种新型的功能性 DNA 纳米结构，它是一种多适体抑制剂，其活性比游离适体高 8 倍。通过单链 DNA 解毒剂也可以逆转凝血酶抑制，从而能够对凝血途径进行显著控制。
