Anticoagulation in the extracorporeal circuit is one of the major challenges in safe and effective hemodialysis treatment. Heparin-like compounds are widely used in clinical hemodialysis procedures. But they still have a range of undesirable side effects and carry a risk of post-treatment bleeding.  

A series of aptamers against thrombin have been screened by systematic evolution of ligands by exponential enrichment (SELEX) technique. These aptamers can directly recognize and inhibit thrombin molecules, while the binding to thrombin can be neutralized through the hybridization of complementary oligonucleotides (antidotes). Several nanoscale anticoagulants based on aptamer-nanoparticle assembly have been reported.  

Recently, a research team led by Prof. DING Baoquan from the National Center for Nanoscience and Technology of the Chinese Academy of Sciences reported a nanoscale anticoagulant aptamer array based on self-assembled DNA origami technology. The study was published in Nature Communications.  

The researchers constructed an anticoagulant aptamer nanoarray on rectangular DNA origami nanostructure. Two different thrombin-binding aptamers were assembled through DNA-hybridization with pre-designed capture sequences on the addressable origami surface. 

The optimized aptamer pattern on DNA origami was found to be necessary for thrombin binding. The origami-aptamer nanoarray initiated thrombin-recognition and activity 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 researchers found that the nanoarray can prolong the circulation time, effectively preventing thrombosis formation. The nanoarray is antidote nucleotides-controlled and immunologically inert in healthy mice.  

Besides, the versatility of the origami-based nanoarray strategy could be further employed to fabricate multiple aptamers that inhibit pro-coagulant proteases in the coagulation pathway for multi-step prevention of blood clotting.  

This DNA origami platform opens a new avenue to bring a safe and effective anticoagulant for the extracorporeal treatment of renal failures and other diseases.