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

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...

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Autores principales: Zhao, Shuai, Tian, Run, Wu, Jun, Liu, Shaoli, Wang, Yuanning, Wen, Meng, Shang, Yingxu, Liu, Qing, Li, Yan, Guo, Ying, Wang, Zhaoran, Wang, Ting, Zhao, Yujing, Zhao, Huiru, Cao, Hui, Su, Yu, Sun, Jiashu, Jiang, Qiao, Ding, Baoquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807036/
https://www.ncbi.nlm.nih.gov/pubmed/33441565
http://dx.doi.org/10.1038/s41467-020-20638-7
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author Zhao, Shuai
Tian, Run
Wu, Jun
Liu, Shaoli
Wang, Yuanning
Wen, Meng
Shang, Yingxu
Liu, Qing
Li, Yan
Guo, Ying
Wang, Zhaoran
Wang, Ting
Zhao, Yujing
Zhao, Huiru
Cao, Hui
Su, Yu
Sun, Jiashu
Jiang, Qiao
Ding, Baoquan
author_facet Zhao, Shuai
Tian, Run
Wu, Jun
Liu, Shaoli
Wang, Yuanning
Wen, Meng
Shang, Yingxu
Liu, Qing
Li, Yan
Guo, Ying
Wang, Zhaoran
Wang, Ting
Zhao, Yujing
Zhao, Huiru
Cao, Hui
Su, Yu
Sun, Jiashu
Jiang, Qiao
Ding, Baoquan
author_sort Zhao, Shuai
collection PubMed
description 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.
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spelling pubmed-78070362021-01-21 A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis Zhao, Shuai Tian, Run Wu, Jun Liu, Shaoli Wang, Yuanning Wen, Meng Shang, Yingxu Liu, Qing Li, Yan Guo, Ying Wang, Zhaoran Wang, Ting Zhao, Yujing Zhao, Huiru Cao, Hui Su, Yu Sun, Jiashu Jiang, Qiao Ding, Baoquan Nat Commun Article 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. Nature Publishing Group UK 2021-01-13 /pmc/articles/PMC7807036/ /pubmed/33441565 http://dx.doi.org/10.1038/s41467-020-20638-7 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhao, Shuai
Tian, Run
Wu, Jun
Liu, Shaoli
Wang, Yuanning
Wen, Meng
Shang, Yingxu
Liu, Qing
Li, Yan
Guo, Ying
Wang, Zhaoran
Wang, Ting
Zhao, Yujing
Zhao, Huiru
Cao, Hui
Su, Yu
Sun, Jiashu
Jiang, Qiao
Ding, Baoquan
A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
title A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
title_full A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
title_fullStr A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
title_full_unstemmed A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
title_short A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
title_sort dna origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807036/
https://www.ncbi.nlm.nih.gov/pubmed/33441565
http://dx.doi.org/10.1038/s41467-020-20638-7
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