Abstract
Nucleic acid aptamers can fold into a multitude three-dimensional structures allowing them to bind to almost any small molecule, nucleic acid or protein target with high specificity and affinity. Aptamers can be generated in a controlled and entirely in vitro process known as SELEX. Advances in aptamer technology have made possible the application of this therapeutic modality to many therapeutic areas including cardiovascular indications. To that end, aptamers have been generated to coagulants, adhesion, and angiogenic targets leading to the pre-clinical and clinical development of numerous aptamer drugs.
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Keywords
- Arterioscl Thromb Vasc Biol
- Vascular Endothelial Cell Growth Factor
- Cardiovascular Therapeutics
- SELEX Process
- Nucleic Acid Aptamers
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References
Bock LC, Griffin LC, Latham JA et al (1995) Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355:564–566
Burmeister PE, Wang C, Killough J R et al (2006) 2B-Deoxy purine, 2–O-methyl pyrimidine (dRmY) aptamers as candidate therapeutics. Oligonucleotides 16(4):337–351
Boncler MA, Koziolkiewicz M, Watala C (2001) Aptamer inhibits degradation of platelet proteolytically activatable receptor, PAR-1, by thrombin. Thromb Res 104:215–222
Chyu K-Y, Shah PK (2007) Choking off plaque neovascularity: a promising atheroprotective strategy or a double-edged sword? Arterioscl Thromb Vasc Biol 27:993–995
Cload ST, McCauley TG, Keefe AD et al (2006) Properties of therapeutic aptamers. In: Klussman S (ed) The aptamer handbook. Wiley, Weinheim, pp 363–416
Dougan H, Lyster DM, Vo CV et al (2000). Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood. Nucl Med Biol 27:289–297
Doyle B, Caplice N (2007) Plaque neovascularization and antiangiogenic therapy for atherosclerosis. J Am Coll Cardiol 49:2102–2104
Dyke CK, Steinhubl SR, Kleiman NS et al (2006) First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology. A Phase Ia pharmacodynamic evaluation of a drug-antidote paior for the controlled regulation of factor IXa activity. Circulation 114:2490–2497
Eyetech Study Group (2003). Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology 110:979–986
Furie B, Furie B (2007) In vivo thrombosis. J Thromb Haemost Suppl 1:12–17
Gilbert JC, DeFeo-Fraulini T, Hutabarat RM et al (2007) Pharmacokinetis, pharmacodynamics, and safety of an anti-von Willebrand factor therapeutic aptamer, ARC1779, in healthy volunteers. Circulation 116:2678–2686
Green LS, Jellinek D, Bell C et al (1995) Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor. Chem Biol 2:683–695
Griffin LC, Tidmarsh GF, Bock LC et al (1993) In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits. Blood 81:3271–3276
Healy JM, Lewis SD, Kurz M et al (2004) Pharmacokinetics and biodistribution of novel aptamer compositions. Pharm Res 21:2234–2246
Hennan JK, Swillo RE, Morgan GA et al (2006) Pharmacologic inhibition of platelet vWF-GPIb alpha interaction prevents coronary artery thrombosis. Thromb Haemost 95:469–475
Huang J, Moore J, Soffer S et al (2001) Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors. J Pediatr Surg 36:357–361
Hutabarat R, Horvath C, Funk WD (2007) Discovery of a potent, direct thrombin inhibiting aptamer, J Thromb Haemost 5(Suppl 2):P-S-067
Italiano JE, Richardson JL, Patel-Hett S Et al (2008) Angiogenesis is regulated by a novel mechanism: Pro- and anti-angiogenic proteins are organized into separate platelet a-granules and differentially released. Blood 111(3):1227–1233 (published ahead of print On-Line October 25, 2007)
Jenison RD, Jennings SD, Walker DW et al (1998) Oligonucleotide inhibitors of P-selectin-dependent neutrophil-platelet adhesion. Antisense Nucleic Acid Drug Dev 8:265–279
Kahlon R, Shapero J, Gotlieb AI (1992) Angiogenesis in atherosclerosis. Can J Cardiol 8:60–64
Kolodgie FD, Narulo J, Yuan C et al (2007) Elimination of neoangiogenesis for plaque stabilization: Is there a role for local drug therapy? J Am Coll Cardiol 49:2093–2101
Lagassé HAD, Merlino PG, Marsh HN et al (2007) Discovery and characterization of a potent neutralizing anti-VWF A1 domain specific aptamer. J Thromb Haemost 5(Suppl 2):P-S-665
Leppanen O, Janjic N, Carlsson M-A et al (2000) Intimal hyperpasia recurs after removal of PDGF-AB and BB inhibition by the rat carotid artery injury model. Arterioscl Thromb Vasc Biol 20:89–95
Li W-X, Kaplan AV, Grant GW et al (1994) A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation. Blood 83:677–682
Michel JB, Thaunat O, Houard X, et al. (2007) Topological determinants and consequences of adventitial responses to arterial wall injury. Arterioscler Thromb Vasc Biol 27:1259–1268
Ng EWM, Adamis AP (2006) Anti-VEGF aptamer (pegaptanib) yherapy for ocular vascular diseases. Oligonucleotide thrapeutics: First Annual Meeting of the Oligonucleotide Therapeutics Society. Ann NY Acad Sci 1082:151–171
Nimjes SM, Keys JR, Pitoc GA et al (2006) A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery. Mol Ther 24:408–415
Nishimura JI, Burnette AD, Oney S et al (2007) Blood 110(11): Abstract 147
Oney S, Nimjee SM, Layzer J et al (2007) Antidote-Controlled Platelet inhibition targeting von Willebrand factor with aptamers. Oligonucleotides 17:265–274
Ostendorf T, Kunter U, Grone HJ et al (2001). Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis. J Am Soc Nephrol 12:909–918
Paborsky LR, McCurdy SN, Griffin LC et al (1993) The single stranded DNA aptamer-binding site of human thrombin. J Biol Chem 268:20808–20811
Petrovan PJ, Kaplan CD, Reisfeld RA et al (2007) DNA vaccination against VEGF receptor 2 reduces atherosclerosis in LDL receptor-deficient mice. Arterioscl Thromb Vasc Biol 27:1095–1100
Rottman RB, Gilbert M, Marsh HN et al (2007) An anti-Von Willebrand’s factor A1 domain aptamer inhibits arterial thrombosis induced by electrical injury in cynomolgus macaques. J Thromb Haemost 5(Suppl 2):P-S-664
Rusconi CP, Yeh A, Lyerly HK et al (2000) Blocking the initiation of coagulation by RNA aptamers to Factor VIIa. Thromb Haemost 84:841–848
Rusconi CP, Roberts JD, Pitoc GA et al (2004a) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnol 22:1423–1428
Rusconi CP, Scardino E, Layzer J et al (2004b) RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 419:90–94
Sarraf-Yazdi S, Mi J, Moeller BJ et al (2007) Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin-2 specific RNA aptamer. J Surg Res (published on-line Oct 22 2007)
Sennino B, Falcon BL, McCauley D et al (2007) Sequential loss of tumor vessel pericytes and endothelial cells after inhibition of platelet-derived growth factor B by selective aptamer AX102. Cancer Res 67:7358–7367
Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510
Wagner-Whyte J, Khuri SF, Preiss JR et al (2007) Discovery of a potent, direct thrombin inhibiting aptamer. J Thromb Haemost 5(Suppl 2):P-S-067
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Pendergrast, P.S., Thompson, K.M., Schaub, R.G. (2008). Nucleic Acid Aptamers for Cardiovascular Therapeutics. In: Erdmann, V.A., Poller, W., Barciszewski, J. (eds) RNA Technologies in Cardiovascular Medicine and Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78709-9_14
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DOI: https://doi.org/10.1007/978-3-540-78709-9_14
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