A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis

Shuai Zhao, Run Tian, Jun Wu, Shaoli Liu, Yuanning Wang, Meng Wen, Yingxu Shang, Qing Liu, Yan Li, Ying Guo, Zhaoran Wang, Ting Wang, Yujing Zhao, Huiru Zhao, Hui Cao, Yu Su, Jiashu Sun, Qiao Jiang () and Baoquan Ding ()
Additional contact information
Shuai Zhao: National Center for Nanoscience and Technology
Run Tian: National Center for Nanoscience and Technology
Jun Wu: Peking University Fourth School of Clinical Medicine
Shaoli Liu: National Center for Nanoscience and Technology
Yuanning Wang: National Center for Nanoscience and Technology
Meng Wen: Peking University Fourth School of Clinical Medicine
Yingxu Shang: National Center for Nanoscience and Technology
Qing Liu: National Center for Nanoscience and Technology
Yan Li: National Center for Nanoscience and Technology
Ying Guo: The Second Affiliated Hospital of Xi’an Jiaotong University
Zhaoran Wang: National Center for Nanoscience and Technology
Ting Wang: National Center for Nanoscience and Technology
Yujing Zhao: Peking University Fourth School of Clinical Medicine
Huiru Zhao: Peking University Fourth School of Clinical Medicine
Hui Cao: Peking University Fourth School of Clinical Medicine
Yu Su: Peking University Fourth School of Clinical Medicine
Jiashu Sun: National Center for Nanoscience and Technology
Qiao Jiang: National Center for Nanoscience and Technology
Baoquan Ding: National Center for Nanoscience and Technology

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-020-20638-7

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