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 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. Safe haemodialysis is essential for patients with acute kidney injury and renal failure. Here the authors present a DNA origami-based approach with high affinity and specificity to thrombin, inhibiting coagulation.

Automated summary

This study presents a promising nanoagent based on DNA origami technology that can effectively prevent thrombosis and exhibit enhanced anticoagulant effects in animal models.