Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In...

Area of Science:

• Biomolecular engineering
• Hemostasis and thrombosis research
• Synthetic biology

Background:

• Unbalanced blood coagulation poses a significant health risk, necessitating precise and rapid therapeutic interventions.
• Current anticoagulant therapies face challenges in reversibility and targeted action.

Purpose of the Study:

• To introduce a novel biomolecular platform using modular RNA-DNA anticoagulant fibers for controlled anticoagulation.
• To develop a "kill-switch" mechanism for reversible hemostasis control.
• To evaluate the efficacy and safety of these anticoagulant fibers.

Main Methods:

• Design and synthesis of RNA-DNA fibers functionalized with thrombin-binding aptamers.
• Assessment of immunoquiescence using human peripheral blood mononuclear cells.
• In vitro and in vivo evaluation of anticoagulant activity and renal clearance in murine and porcine models.
• Testing of the "kill-switch" mechanism for hemostasis restoration.

Main Results:

• The anticoagulant fibers demonstrated effective and reversible anticoagulation by targeting thrombin.
• Fibers exhibited superior anticoagulant activity and prolonged renal clearance compared to free aptamers.
• The "kill-switch" mechanism successfully restored hemostasis in vivo.
• The platform showed no adverse immune response in human cell assays.

Conclusions:

• The developed RNA-DNA anticoagulant fibers represent a user-friendly and reconfigurable platform for precise anticoagulation control.
• The integrated "kill-switch" mechanism offers a safe and effective way to reverse anticoagulation and restore hemostasis.
• This technology holds significant potential for treating coagulation disorders and managing bleeding events.