A Mini-Review: Clinical Development and Potential of Aptamers for Thrombotic Events Treatment and Monitoring

Abstract

The unique opportunity for aptamer uses in thrombotic events has sparked a considerable amount of research in the area. The short half-lives of unmodified aptamers in vivo remain one of the major challenges in therapeutic aptamers. Much of the incremental successful therapeutic aptamer stories were due to modifications in the aptamer bases. This mini-review briefly summarizes the successes and challenges in the clinical development of aptamers for thrombotic events, and highlights some of the most recent developments in using aptamers for anticoagulation monitoring.

Keywords: DNA; RNA; SELEX; aptamer; molecular recognition element (MRE); monitoring; thrombotic event; treatment.

Figure 1

Illustration of the basic Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process. Repeated cycles of target–library incubation, partitioning, and amplification are performed to enrich the library’s overall affinity toward the target of interest.

Figure 2

Illustration of the coagulation cascade upon vascular endothelium injury. Aptamers have been isolated to inhibit clotting factors in both the extrinsic and intrinsic pathways of the coagulation cascade. Different inhibition stages ultimately lead to the inhibition of insoluble fibrin (Factor Ia) formation. The blue cloud shapes represent aptamers that have been identified to inhibit specific clotting factors. Each Roman numeral represents the corresponding clotting factor.

Figure 3

Illustration of the clotting cascade upon vascular endothelium injury. VWF: Von Willebrand factor; ADP: adenosine diphosphate. VWF and collagen activate platelets. Upregulated GPIIb/IIIa receptors on activated platelets increase the release of thromboxane A2 and ADP, and additional platelets are activated to promote clot formation at the site of injury. The blue cloud shape represents aptamers that have been identified to inhibit the Von Willebrand factor and stops platelet activation.

Figure 4

The structure of thrombin interaction with the 15-mer DNA aptamer (PDB 1HUT or NDB PDE013) [53].