APTAMERS ARE NEW PHARMACOLOGICAL SUBSTANCES FOR THE DEVELOPMENT OF ANTICOAGULANTS
https://doi.org/10.21518/2307-1109-2017-1-134-144
Abstract
A ptamers are a new class of oligonucleotide compounds capable of specific binding to various molecular targets and inhibiting their activity. Aptamers are selected from a library of randomly syn-thesized oligonucleotides (from 20 to 60 nucleotides long) based on their ability to bind to the target molecule. In the future, such primary aptamers can be chemically modified to optimize their structure and increase stability. Aptamers are considered to be chemical (oligonucleotide) analogues of monoclonal antibodies: their specificity is similar to that of antibodies, and they have high affinity to their targets. Aptamers are widely used to create pharmacological medicines. As pharmacological substances, they have a number of benefits over antibodies and other protein molecules. Aptamers are practically non-immunogenic, chemically synthesized without the use of biological producers, and their antidotes can easily be created using complementary sequences. The review highlights reports devoted to the development of new anticoagulant aptamer-based medications. The most detailed studies, both preclinical and clinical (various phases of clinical trials), were performed in relation to the study of aptamers against vWF, factor IX and thrombin.
About the Authors
A. V. Mazurov
MD, Prof.
Russian Federation
Russian Federation
Russian Cardiology Research and Production Complex, MoH RF
V. A. Spiridonova
A.N. Belozersky Institute of Physico-Chemical Biology; Lomonosov
Moscow State University
Russian Federation
Russian Federation
References
1. Keefe AD, Pai S, Ellington A. Aptamers as therapeutics. Nat Rev Drug Discov, 2010, 9: 537-550.
2. Ni X, Castanares M, Mukherjee A, Lupold SE. Nucleic acid aptamers: clinical applications and promising new horizons. Curr Med Chem, 2011, 18: 4206–4214.
3. Kadioglu O, Malczyk AH, Greten HJ, Efferth T. Aptamers as a novel tool for diagnostics and therapy. Invest New Drugs, 2015, DOI 10.1007/s10637-015-0213-y.
4. Li W, Wang K, Zhao M, Yang X, Chen M, Lan X. Development of aptamer oligonucleotides as anticoagulants and antithrombotics for cardiovascular diseases: current status. Thromb Res, 2014, 134: 769–773.
5. Мазуров А.В. Физиология и патология тромбоцитов. М.: Литтерра, 2011: 79-84.
6. Cosmi B. ARC-1779, a PEGylated aptamer antagonist of von Willebrand factor for potential use as an anticoagulant or antithrombotic agent. Curr Opin Mol. Ther., 2009, 11: 322-328.
7. Diener JL, Daniel LagassО, HA, Duerschmied D, Merhi Y, Tanguay JF, Hutabarat R, Gilbert J, Wagner DD, Schaub R. Inhibition of von Willebrand factor mediated platelet activation and thrombosis by the anti von Willebrand factor A1-domain aptamer ARC1779. J Thromb Haemost, 2009, 7: 1155-1162.
8. Arzamendi D, Dandachli F, ThОorРt JF, Ducrocq G, Chan M, Mourad W, Gilbert JC, Schaub RG, Tanguay JF, Merhi Y. An anti-von Willebrand factor aptamer reduces platelet adhesion among patients receiving aspirin and clopidogrel in an ex vivo shear-induced arterial thrombosis. Clin Appl Thromb Hemost, 2011: 17, E70-E78.
9. Gilbert JC, DeFeo-Fraulini T, Hutabarat RM, Horvath CJ, Merlino PG, Marsh HN, Healy JM, Boufakhreddine S, Holohan TV, Schaub RG. First-in-human evaluation of anti–von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Circulation, 2007, 116: 2678-2686.
10. Tsai H-M. Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. In: Platelets. Third Edition. (ed. Michelson AD). Amsterdam, Boston, Heidelberg et al: Academic Press, Elsevier Inc. 2013. pp. 883-908.
11. Мазуров А.В. Физиология и патология тромбоцитов. М.: Литтерра, 2011: 291-301.
12. Cataland SR, Peyvandi F, Mannucci PM, Lammle B, Kremer Hovinga JA, Machin SJ, Scully M, Rock G, Gilbert JC, Yang S, Wu H, Jilma B, Knoebl P. Initial experience from a double-blind, placebo-controlled, clinical outcome study of ARC1779 in patients with thrombotic thrombocytopenic purpura. Am J Hematol, 2012, 87: 430-432.
13. Jilma-Stohlawetz P, KnЪbl P, Gilbert JC, Jilma B. The anti-von Willebrand factor aptamer ARC1779 increases von Willebrand factor levels and platelet counts in patients with type 2B von Willebrand disease. Thromb Haemost, 2012, 108: 284-290.
14. Markus HS, McCollum C, Imray C., Goulder MA, Gilbert J, King A. The von Willebrand inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy: a randomized trial. Stroke, 2011, 42: 2149-2153.
15. Smith SB, Gailani D. Update on the physiology and pathology of factor IX activation by factor XIa. Expert Rev Hematol, 2008, 1: 87–98.
16. Dyke CK, Steinhubl SR, Kleiman NS, Cannon RO, Aberle LG, Lin M, Myles SK, Melloni C, Harrington RA, Alexander JH, Becker RC, Rusconi CP. First-inhuman 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: 2490-2497.
17. Rusconi CP1, Roberts JD, Pitoc GA, Nimjee SM, White RR, Quick G Jr, Scardino E, Fay WP, Sullenger BA. Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnology, 2004, 22: 1423-1428.
18. Nimjee SM, Keys JR, Pitoc GA, Quick G, Rusconi CP, Sullenger BA. A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery. Mol Ther, 2006, 14: 408-415.
19. Chan MY, Cohen MG, Dyke CK, Myles SK, Aberle LG, Lin M, Walder J, Steinhubl SR, Gilchrist IC, Kleiman NS, Vorchheimer DA, Chronos N, Melloni C, Alexander JH, Harrington RA, Tonkens RM, Becker RC, Rusconi CP. 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. Cohen MG, Purdy DA, Rossi JS, Grinfeld LR, Myles SK, Aberle LH, Greenbaum AB, Fry E, Chan MY,
Review
For citations:
Mazurov A.V., Spiridonova V.A. APTAMERS ARE NEW PHARMACOLOGICAL SUBSTANCES FOR THE DEVELOPMENT OF ANTICOAGULANTS. Aterotromboz = Atherothrombosis. 2017;(1):134-144. (In Russ.) https://doi.org/10.21518/2307-1109-2017-1-134-144
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