RSS-Feed abonnieren
DOI: 10.1160/TH09-10-0716
Nucleic acid aptamers as antithrombotic agents: Opportunities in extracellular therapeutics
Publikationsverlauf
Received:
21. Oktober 2009
Accepted after minor revision:
17. Februar 2009
Publikationsdatum:
22. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201003/lookinside/thumbnails/10-1160-th09-10-0716-1.jpg)
Summary
Antithrombotic therapy for the acute management of thrombotic disorders has been stimulated and guided actively by our current understanding of platelet biology, coagulation proteases, and vascular science. A translatable platform for coagulation, based soundly on biochemistry, enzymology and cellular events on platelets and tissue factor-baring cells, introduces fundamental constructs, mechanistic clarity, and an unparalleled opportunity for accelerating the development and clinical investigation of both disease- and patient-specific therapies. In the current review, we build upon and expand substantially our observations surrounding nucleic acids as antithrombotic agents.
-
References
- 1 Becker RC, Rusconi C, Sullenger B. Nucleic acid aptamers in therapeutic anticoagulation. Technology, development and clinical application. Thromb Haemost 2005; 93: 1014-1020.
- 2 Dausse E. et al. In vitro selection procedures for identifying DNA and RNA aptamers targeted to nucleic acids and proteins. Methods Mol Biol 2005; 288: 391-410.
- 3 Rimmele M. Nucleic acid aptamers as tools and drugs: recent developments. Chembiochem 2003; 4: 963-971.
- 4 Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990; 249: 505-510.
- 5 Dua P, Kim S, Lee DK. Patents on SELEX and therapeutic aptamers. Recent Pat DNA Gene Seq 2008; 2: 172-186.
- 6 Gopinath SC. Methods developed for SELEX. Anal Bioanal Chem 2007; 387: 171-182.
- 7 Watrin M. et al. Aptamers targeting RNA molecules. Methods Mol Biol 2009; 535: 79-105.
- 8 Rusconi CP. et al. Blocking the initiation of coagulation by RNA aptamers to factor VIIa. Thromb Haemost 2000; 84: 841-848.
- 9 Doudna JA, Cech TR, Sullenger BA. Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor. Proc Natl Acad Sci USA 1995; 92: 2355-2359.
- 10 Lee SW, Sullenger BA. Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies. Nat Biotechnol 1997; 15: 41-45.
- 11 Renner S. et al. Maximum common binding modes (MCBM): consensus docking scoring using multiple ligand information and interaction fingerprints. J Chem Inf Model 2008; 48: 319-332.
- 12 Wu G, Vieth M. SDOCKER: a method utilizing existing X-ray structures to improve docking accuracy. J Med Chem 2004; 47: 3142-3148.
- 13 Monroe DM. Platelets and Thrombin Generation. Arterioscler Thromb Vasc Biol 2002; 22: 1381-1389.
- 14 Rusconi CP. et al. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 2002; 419: 90-94.
- 15 Rusconi CP. et al. Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnol 2004; 22: 1423-1428.
- 16 Nimjee SM. et al. A Novel Antidote-Controlled Anticoagulant Reduces Thrombin Generation and Inflammation and Improves Cardiac Function in Cardiopulmonary Bypass Surgery. Mol Ther 2006; 14: 408-415.
- 17 Tanaka KA. et al. In-vitro evaluation of anti-factor IXa aptamer on thrombin generation, clotting time, and viscoelastometry. Thromb Haemost 2009; 101: 827-833.
- 18 Dyke CK. et al. First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity. Circulation 2006; 114: 2490.
- 19 Chan MY. et al. Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. Circulation 2008; 117: 2865-2874.
- 20 Chan MY. et al. A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor. J Thromb Haemost 2008; 6: 789-796.
- 21 Cohen MG. et al. First clinical application of an actively reversible direct factor IXa inhibitor in elective percutaneous coronary intervention. Eur Heart J. 2009 30. 101 (Abstract Supplement)
- 22 Bock LC. et al. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 1992; 355: 564-566.
- 23 Griffin LC. et al. In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits. Blood 1993; 81: 3271-3276.
- 24 Li WX. et al. A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation. Blood 1994; 83: 677-682.
- 25 DeAnda Jr A. et al. Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass. Ann Thorac Surg 1994; 58: 344-350.
- 26 Tasset DM, Kubik MF, Steiner W. Oligonucleotide inhibitors of human thrombin that bind distinct epitopes. J Mol Biol 1997; 272: 688-698.
- 27 Holland CA. et al. Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin. FEBS Lett 2000; 484: 87-91.
- 28 Gatto B. et al. Nucleic acid aptamers based on the G-quadruplex structure: therapeutic and diagnostic potential. Curr Med Chem 2009; 16: 1248-1265.
- 29 Long SB. et al. Crystal structure of an RNA aptamer bound to thrombin. RNA 2008; 14: 2504-2512.
- 30 Muller J. et al. Anticoagulant characteristics of HD1–22, a bivalent aptamer that specifically inhibits thrombin and prothrombinase. J Thromb Haemost 2008; 6: 2105-2112.
- 31 Andrews RK. et al. Glycoprotein Ib-IX-V. Int J Biochem Cell Biol 2003; 35: 1170-1174.
- 32 Hodivala-Dilke KM. et al. Beta3-integrin-deficient mice are a model for Glanz-mann thrombasthenia showing placental defects and reduced survival. J Clin Invest 1999; 103: 229-238.
- 33 Smyth SS. et al. Variable protection of beta 3-integrin--deficient mice from thrombosis initiated by different mechanisms. Blood 2001; 98: 1055-1062.
- 34 Ware J. et al. Generation and rescue of a murine model of platelet dysfunction: the Bernard-Soulier syndrome. Proc Natl Acad Sci USA 2000; 97: 2803-2808.
- 35 Oney S. et al. Antidote-Controlled Platelet Inhibition Targeting von Willebrand Factor with Aptamers. Oligonucleotides 2007; 17: 265-274.
- 36 Gilbert JC. et al. First-in-Human Evaluation of Anti von Willebrand Factor Therapeutic Aptamer ARC1779 in Healthy Volunteers. Circulation 2007; 116: 2678-2686.
- 37 Grossman SA. et al. Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas. Neuro Oncol 2005; 7: 32-40.