Antidote control of aptamer therapeutics: The road to a safer class of drug agents

Current Pharmaceutical Biotechnology

Volumn 13, Issue 10, 2012, Pages 1924-1934

  Bompiani, K M ^a   Woodruff, R S ^a   Becker, R C ^a   Nimjee, S M ^a   Sullenger, B A ^a  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Anticoagulant; Antidote; Antiplatelet; Aptamer; Oligonucleotide antidote; Therapeutic; Universal antidote

Indexed keywords

ANTICOAGULANT AGENT; ANTIDOTE; APTAMER; CYCLODEXTRIN; OLIGONUCLEOTIDE; SERINE PROTEINASE; SERINE PROTEINASE FIX; UNCLASSIFIED DRUG; VON WILLEBRAND FACTOR;

ARTICLE; COST EFFECTIVENESS ANALYSIS; CRYSTAL STRUCTURE; HUMAN; NONHUMAN; NONVIRAL GENE THERAPY; PATENT; THROMBOSIS;

ANIMALS; ANTICOAGULANTS; ANTIDOTES; APTAMERS, NUCLEOTIDE; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; LIGANDS; MODELS, MOLECULAR; PLATELET AGGREGATION INHIBITORS; PROTEIN BINDING; PROTEIN CONFORMATION; SELEX APTAMER TECHNIQUE;

EID: 84866693789     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/138920112802273137     Document Type: Article

References (57)

1. Sullenger, B.A.; Gallardo, H.F.; Ungers, G.E.; Gilboa, E. Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell, 1990, 63(3), 601-608.
2. Ellington, A.D.; Szostak, J.W. In vitro selection of RNA molecules that bind specific ligands. Nature, 1990, 346(6287), 818-822.
3. Tuerk, C.; Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science, 1990, 249(4968), 505-510.
4. Nimjee, S.M.; Rusconi, C.P.; Sullenger, B.A. Aptamers: an emerging class of therapeutics. Annu. Rev. Med., 2005, 56 555-583.
5. Ng, E.W.; Shima, D.T.; Calias, P.; Cunningham, E.T., Jr.; Guyer, D.R.; Adamis, A.P. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat. Rev. Drug Discov., 2006, 5(2), 123-132.
6. Dyke, C.K.; Steinhubl, S.R.; Kleiman, N.S.; Cannon, R.O.; Aberle, L.G.; Lin, M.; Myles, S.K.; Melloni, C.; Harrington, R.A.; Alexander, J.H.; Becker, R.C.; Rusconi, C.P. 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(23), 2490-2497.
7. Nimjee, S.M.; Keys, J.R.; Pitoc, G.A.; Quick, G.; Rusconi, C.P.; Sullenger, B.A. A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery. Mol. Ther., 2006, 14(3), 408-415.
8. Rusconi, C.P.; Roberts, J.D.; Pitoc, G.A.; Nimjee, S.M.; White, R.R.; Quick, G., Jr.; Scardino, E.; Fay, W.P.; Sullenger, B.A. Antidote-mediated control of an anticoagulant aptamer in vivo. Nat. Biotechnol., 2004, 22(11), 1423-1428.
9. Rusconi, C.P.; Scardino, E.; Layzer, J.; Pitoc, G.A.; Ortel, T.L.; Monroe, D.; Sullenger, B.A. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature, 2002, 419(6902), 90-94.
10. Oney, S.; Nimjee, S.M.; Layzer, J.; Que-Gewirth, N.; Ginsburg, D.; Becker, R.C.; Arepally, G.; Sullenger, B.A. Antidote-controlled platelet inhibition targeting von Willebrand factor with aptamers. Oligonucleotides, 2007, 17(3), 265-274.
11. Oney, S.; Lam, R.T.; Bompiani, K.M.; Blake, C.M.; Quick, G.; Heidel, J.D.; Liu, J.Y.; Mack, B.C.; Davis, M.E.; Leong, K.W.; Sullenger, B.A. Development of universal antidotes to control aptamer activity. Nat. Med., 2009, 15(10), 1224-1228.
12. Long, S.B.; Long, M.B.; White, R.R.; Sullenger, B.A. Crystal structure of an RNA aptamer bound to thrombin. RNA, 2008, 14 1-9.
13. Buddai, S.K.; Layzer, J.M.; Lu, G.; Rusconi, C.P.; Sullenger, B.A.; Monroe, D.M.; Krishnaswamy, S. An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase. J. Biol. Chem., 2009.
14. Chan, M.Y.; Rusconi, C.P.; Alexander, J.H.; Tonkens, R.M.; Harrington, R.A.; Becker, R.C. A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor. J. Thromb. Haemost., 2008, 6(5), 789-796.
15. Group, T.E.S. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology, 2003, 110(5), 979-986.
16. Rimmele, M. Nucleic acid aptamers as tools and drugs: recent developments. Chembiochem., 2003, 4(10), 963-971.
17. White, R.; Rusconi, C.; Scardino, E.; Wolberg, A.; Lawson, J.; Hoffman, M.; Sullenger, B. Generation of species cross-reactive aptamers using "toggle" SELEX. Mol. Ther., 2001, 4(6), 567-573.
18. Morris, K.N.; Jensen, K.B.; Julin, C.M.; Weil, M.; Gold, L. High affinity ligands from in vitro selection: complex targets. Proc. Natl. Acad Sci. USA, 1998, 95(6), 2902-2907.
19. Keefe, A.D.; Cload, S.T. SELEX with modified nucleotides. Curr. Opin. Chem. Biol., 2008, 12(4), 448-456.
20. Rusconi, C.P.; Yeh, A.; Lyerly, H.K.; Lawson, J.H.; Sullenger, B.A. Blocking the initiation of coagulation by RNA aptamers to factor VIIa. Thromb. Haemost., 2000, 84(5), 841-848.
21. Pieken, W.A.; Olsen, D.B.; Benseler, F.; Aurup, H.; Eckstein, F. Kinetic characterization of ribonuclease-resistant 2'-modified hammerhead ribozymes. Science, 1991, 253(5017), 314-317.
22. Healy, J.M.; Lewis, S.D.; Kurz, M.; Boomer, R.M.; Thompson, K.M.; Wilson, C.; McCauley, T.G. Pharmacokinetics and biodistribution of novel aptamer compositions. Pharm. Res., 2004, 21(12), 2234-2246.
23. Boomer, R.M.; Lewis, S.D.; Healy, J.M.; Kurz, M.; Wilson, C.; McCauley, T.G. Conjugation to polyethylene glycol polymer promotes aptamer biodistribution to healthy and inflamed tissues. Oligonucleotides, 2005, 15(3), 183-195.
24. Rusconi C.; K.D. Zelenkofske. Subcutaneous FIXa inhibitor provides prolonged anticoagulation: The first successful subcutaneous application of an aptamer. J. Am Coll. Cardiol. 2010; Vol. 55, p A172. E1618.
25. Thiel, K. Oligo oligarchy-the surprisingly small world of aptamers. Nature biotechnology, 2004, 22(6), 649-651.
26. Gold, L.; Tuerk, C. Nucleic acid ligands. U.S. Patent 5,670,637, September 23, 1997.
27. NIH. Clinical Trials. Available at: http://clinicaltrials.gov (Accessed March 16, 2011).
28. Nimjee, S.M.; Rusconi, C.P.; Harrington, R.A.; Sullenger, B.A. The potential of aptamers as anticoagulants. Trends Cardiovasc. Med., 2005, 15(1), 41-45.
29. Becker, R.C.; Oney, S.; Becker, K.C.; Rusconi, C.P.; Sullenger, B. Nucleic acid aptamers and their complimentary antidotes. Entering an era of antithrombotic pharmacobiologic therapy. Hamostaseologie, 2007, 27(5), 378-382.
30. Carr, J.A.; Silverman, N. The heparin-protamine interaction. A review. The Journal of cardiovascular surgery, 1999, 40(5), 659-666.
31. Yavari, M.; Becker, R.C. Anticoagulant therapy during cardiopulmonary bypass. J. Thromb. Thrombol., 2008, 26(3), 218-228.
32. Warkentin, T.E. Heparin-induced thrombocytopenia: a clinicopathologic syndrome. Thromb. Haemost., 1999, 82(2), 439-447.
33. Becker, R.C.; Rusconi, C.; Sullenger, B. Nucleic acid aptamers in therapeutic anticoagulation. Technology, development and clinical application. Thromb. Haemost., 2005, 93(6), 1014-1020.
34. Griffin, L.C.; Tidmarsh, G.F.; Bock, L.C.; Toole, J.J.; Leung, L.L. In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits. Blood, 1993, 81(12), 3271-3276.
35. DeAnda, A., Jr.; Coutre, S.E.; Moon, M.R.; Vial, C.M.; Griffin, L.C.; Law, V.S.; Komeda, M.; Leung, L.L.; Miller, D.C. Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass. The Ann. Thora. Surg., 1994, 58(2), 344-350.
36. Schwienhorst, A. Direct thrombin inhibitors-a survey of recent developments. Cell Mol. Life Sci., 2006, 63(23), 2773-2791.
37. Becker, R.C.; Povsic, T.; Cohen, M.G.; Rusconi, C.P.; Sullenger, B. Nucleic acid aptamers as antithrombotic agents: Opportunities in extracellular therapeutics. Thromb. Haemost., 103(3), 586-595.
38. Chan, M.Y.; Cohen, M.G.; Dyke, C.K.; Myles, S.K.; Aberle, L.G.; Lin, M.; Walder, J.; Steinhubl, S.R.; Gilchrist, I.C.; Kleiman, N.S.; Vorchheimer, D.A.; Chronos, N.; Melloni, C.; Alexander, J.H.; Harrington, R.A.; Tonkens, R.M.; Becker, R.C.; Rusconi, C.P. Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. Circulation, 2008, 117(22), 2865-2874.
39. Group, T.E.S. Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina (Philadelphia, Pa, 2002, 22(2), 143-152.
40. Gilbert, J.C.; DeFeo-Fraulini, T.; Hutabarat, R.M.; Horvath, C.J.; Merlino, P.G.; Marsh, H.N.; Healy, J.M.; Boufakhreddine, S.; Holohan, T.V.; Schaub, R.G. First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Circulation, 2007, 116(23), 2678-2686.
41. Spiel, A.O.; Mayr, F.B.; Ladani, N.; Wagner, P.G.; Schaub, R.G.; Gilbert, J.C.; Jilma, B. The aptamer ARC1779 is a potent and specific inhibitor of von Willebrand Factor mediated ex vivo platelet function in acute myocardial infarction. Platelets, 2009, 20(5), 334-340.
42. Hoffman, M.; Monroe, D.M.; Oliver, J.A.; Roberts, H.R. Factors IXa and Xa play distinct roles in tissue factor-dependent initiation of coagulation. Blood, 1995, 86(5), 1794-1801.
43. Schmidt, A.E.; Bajaj, S.P. Structure-function relationships in factor IX and factor IXa. Trends Cardiovasc. Med., 2003, 13(1), 39-45.
44. Hoffman, M.; Monroe, D.M., A cell-based model of hemostasis. Thromb. Haemost., 2001, 85(6), 958-965.
45. Cohen, M.G., Purdy DA, Rossi JS, Grinfeld LR, Aberle LH, Greenbaum AB, Fry ET, Alexander JH, Rusconie CP, Becker RC First in clinical application of an actively reversible direct factor IXa inhibitor in elective percutaneous coronary intervention. European Heart J., 2009, 30(101).
46. Zelenkofske SL, Damiento CM, Wargin W, Medlock M, Becker R In Subcutaneous RB006, a direct FIXa inhibitor provides prolonged anticoagulation with rapid reversal; the first clinical experience with the REG2 system, Atherothrombosis and Vascular Biology Meeting, April, 2010.
47. Huynh, T.; Theroux, P.; Bogaty, P.; Nasmith, J.; Solymoss, S. Aspirin, warfarin, or the combination for secondary prevention of coronary events in patients with acute coronary syndromes and prior coronary artery bypass surgery. Circulation, 2001, 103(25), 3069-3074.
48. Andrews, R.K.; Gardiner, E.E.; Shen, Y.; Whisstock, J.C.; Berndt, M.C. Glycoprotein Ib-IX-V. Int. J. Biochem. Cell Biol., 2003, 35(8), 1170-1174.
49. Ruggeri, Z.M. Von Willebrand factor, platelets and endothelial cell interactions. J. Thromb. Haemost., 2003, 1(7), 1335-1342.
50. Kleinman, M.E.; Yamada, K.; Takeda, A.; Chandrasekaran, V.; Nozaki, M.; Baffi, J.Z.; Albuquerque, R.J.; Yamasaki, S.; Itaya, M.; Pan, Y.; Appukuttan, B.; Gibbs, D.; Yang, Z.; Kariko, K.; Ambati, B.K.; Wilgus, T.A.; DiPietro, L.A.; Sakurai, E.; Zhang, K.; Smith, J.R.; Taylor, E.W.; Ambati, J. Sequence-and targetindependent angiogenesis suppression by siRNA via TLR3. Nature, 2008, 452(7187), 591-597.
51. Davis, J.T. G-quartets 40 years later: from 5'-GMP to molecular biology and supramolecular chemistry. Angew. Chem. Int. Ed. Engl., 2004, 43(6), 668-698.
52. Padmanabhan, K.; Padmanabhan, K.P.; Ferrara, J.D.; Sadler, J.E.; Tulinsky, A. The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer. J. Biol. Chem., 1993, 268(24), 17651-17654.
53. Joachimi, A.; Mayer, G.; Hartig, J.S. A new anticoagulant-antidote pair: control of thrombin activity by aptamers and porphyrins. J. Am. Chem. Soc., 2007, 129(11), 3036-3037.
54. Mao, H.Q.; Leong, K.W. Design of Polyphosphoester-DNA Nanoparticles for Non-Viral Gene Delivery. Adv. Genet., 2005, 53PA 275-306.
55. Davis, M.E.; Brewster, M.E. Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug. Discov., 2004, 3(12), 1023-1035.
56. Gonzalez, H.; Hwang, S.J.; Davis, M.E. New class of polymers for the delivery of macromolecular therapeutics. Bioconjug. Chem., 1999, 10(6), 1068-1074.
57. Davis, M.E.; Pun, S.H.; Bellocq, N.C.; Reineke, T.M.; Popielarski, S.R.; Mishra, S.; Heidel, J.D. Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymers. Curr. Med. Chem., 2004, 11(2), 179-197.