Modulation of the Coagulation Cascade Using Aptamers

Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2083-91. doi: 10.1161/ATVBAHA.115.300131. Epub 2015 Aug 27.

Abstract

As a novel class of therapeutics, aptamers, or nucleic acid ligands, have garnered clinical interest because of the ease of isolating a highly specific aptamer against a wide range of targets, their chemical flexibility and synthesis, and their inherent ability to have their function reversed. The following review details the development and molecular mechanisms of aptamers targeting specific proteases in the coagulation cascade. The ability of these anticoagulant aptamers to bind to and inhibit exosite function rather than binding within the active site highlights the importance of exosites in blocking protein function. As both exosite inhibitors and reversible agents, the use of aptamers is a promising strategy for future therapeutics.

Keywords: anticoagulation; aptamer; coagulation cascade; nucleic acids; serine endopeptidases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aptamers, Nucleotide / pharmacology
  • Aptamers, Nucleotide / therapeutic use*
  • Blood Coagulation / drug effects*
  • Blood Coagulation / genetics
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Female
  • Humans
  • Male
  • Molecular Targeted Therapy / methods*
  • Prothrombin / drug effects
  • Prothrombin / metabolism
  • Sensitivity and Specificity
  • Serine Endopeptidases / drug effects
  • Serine Endopeptidases / metabolism
  • Thrombin / drug effects
  • Thrombin / metabolism

Substances

  • Aptamers, Nucleotide
  • Prothrombin
  • Serine Endopeptidases
  • Thrombin