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 (NCNST) reported a nanoscale anticoagulant aptamer array based on self-assembled DNA origami technology. The results were published in Nature Communications.
An anticoagulant aptamer nanoarray on rectangular DNA origami nanostructure was constructed. 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 nanoarray can prolong the circulation time, effectively preventing thrombosis formation. The nanoarray is antidote nucleotides-controlled and immunologically inert in healthy mice.
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.
his DNA origami platform will open a new avenue to bring a safe and effective anticoagulant for the extracorporeal treatment of renal failures and other diseases.
This work was supported by the Beijing Municipal Science & Technology Commission, the National Natural Science Foundation of China, the Key Research Program of Frontier Sciences, CAS, and the Strategic Priority Research Program of Chinese Academy of Sciences.
Figure 1 Design of an aptamer-functionalized DNA origami nanoarray for anticoagulation