CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China.
University of Chinese Academy of Sciences, 100049, Beijing, China.
Nat Commun. 2021 Jan 13;12(1):358. doi: 10.1038/s41467-020-20638-7.
Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.
有效的和安全的血液透析对急性肾损伤和慢性肾衰竭患者至关重要。然而，开发在血液透析过程中使用的有效抗凝剂和安全解毒剂已被证明具有挑战性。在这里，我们描述了基于 DNA 折纸的组装体，这些组装体能够抑制凝血酶活性和血栓形成。两种不同的凝血酶结合适体修饰的 DNA 折纸引发蛋白识别和抑制，在人血浆、新鲜全血和小鼠模型中表现出增强的抗凝作用。在包含模拟临床血液透析的透析器的体外回路中，基于折纸的适体纳米阵列有效地防止了血栓形成。含有与凝血酶结合适体互补序列的寡核苷酸可以有效地中和抗凝作用。该纳米阵列在健康小鼠中是安全的且免疫惰性的，不会引起肝脏和肾脏功能或血清细胞因子浓度的任何可检测变化。这种基于 DNA 折纸的纳米试剂代表了一种有前途的抗凝平台，可用于治疗肾脏疾病的血液透析。
