Aptamers as therapeutics in cardiovascular diseases

Abstract

With many advantages over other therapeutic agents such as monoclonal antibodies, aptamers have recently emerged as a novel and powerful class of ligands with excellent potential for diagnostic and therapeutic applications. Typically generated through Systematic Evolution of Ligands by EXponential enrichment (SELEX), aptamers have been selected against a wide range of targets such as proteins, phospholipids, sugars, nucleic acids, as well as whole cells. DNA/RNA aptamers are single-stranded DNA/RNA oligonucleotides (with a molecular weight of 5-40 kDa) that can fold into well-defined 3D structures and bind to their target molecules with high affinity and specificity. A number of strategies have been adopted to synthesize aptamers with enhanced in vitro/in vivo stability, aiming at potential therapeutic/diagnostic applications in the clinic. In cardiovascular diseases, aptamers can be developed into therapeutic agents as anti-thrombotics, anti-coagulants, among others. This review focuses on aptamers that were selected against various molecular targets involved in cardiovascular diseases: von Willebrand factor (vWF), thrombin, factor IX, phospholamban, P-selectin, platelet-derived growth factor, integrin α(v)β(3), CXCL10, vasopressin, among others. With continued effort in the development of aptamer-based therapeutics, aptamers will find their niches in cardiovascular diseases and significantly impact clinical patient management.

Fig. (1)

Crystal structure of the all-DNA parent of ARC1779 bound to the A1 domain of von Willebrand factor (vWF). Adapted from [3].

Fig. (2)

Structural models of the complex of thrombin binding aptamer (TBA) or modified thrombin binding aptamer (mTBA) with two thrombin molecules. The interacting residues of exosite I (green) and exosite II (cyan) are shown. Adapted from [51].

Fig. (3)

REG1 is an anti-coagulation system that includes a factor IXa-specific aptamer (RB006) and its oligonucleotide antidote (RB007).