Editors' ChoiceHEMATOLOGY

Folding DNA to foil the clotting cascade

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Science Translational Medicine  27 Jan 2021:
Vol. 13, Issue 578, eabg5636
DOI: 10.1126/scitranslmed.abg5636

Abstract

Origami-inspired DNA aptamer arrays prevent blood clotting in hemodialysis circuits.

Safe, effective, and reversible inhibition of coagulation is critical for a variety of medical device–based therapies. Current hemodialysis and extracorporeal membrane oxygenation circuits mostly use heparin formulations to prevent blood clotting during treatment. Despite recent improvements in heparin formulations, there remains a need for effective and reversible anticoagulation alternatives to improve the safety profile of hemodialysis and other blood treatments.

One approach to inhibiting the coagulation cascade is to competitively bind thrombin, and DNA aptamers for this purpose have previously been described. Practical use of these aptamers has been limited because delivery, degradation, and clearance issues. In a recent study, Zhao et al. sought to develop stable DNA aptamer arrays (aptarrays) that can bind and inactivate thrombin as it passes over a surface.

The authors used an origami-inspired approach to capture and fold DNA aptamers on surfaces. They used a mixture of staple and capture DNA strands to create a rectangular base that can hybridize with thrombin-binding aptamers. With extensive characterization experiments, they showed that the resulting aptarrays efficiently inhibited coagulation in ex vivo human blood and in mice. Additionally, the anticoagulation effect could be rapidly reversed with a complementary DNA strand antidote that restored thrombin circulation and function.

The aptarrays can be patterned on dialysis and other blood circuit devices to prevent clotting in extracorporeal therapies. This approach could be further developed to incorporate other pharmacologically active aptamers or to bind reactive oxygen species, resulting in a new class of therapeutic surfaces. Researchers now have an approach to reversibly inhibit coagulation when blood comes into contact with medical devices. Further studies will be needed to establish the safety of the aptarrays in larger animal models and in people and to define possible immunologic effects.

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