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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Aptamer Oligonucleotides as Potential Therapeutics in Hematologic Diseases

Author(s): Weibin Li, Meng Zhao, Huihui Yan, Kaiyu Wang and XIaopeng lan*

Volume 19, Issue 10, 2019

Page: [788 - 795] Pages: 8

DOI: 10.2174/1389557517666171002160526

Price: $65

Abstract

Aptamers are single-stranded DNA or RNA oligonucleotides generated by a novel in vitro selection technique termed Systematic evolution of ligands by exponential enrichment (SELEX). During the past two decades, various aptamer drugs have been developed and many of them have entered into clinical trials.

In the present review, we focus on aptamers as potential therapeutics for hematological diseases, including anemia of chronic inflammation (ACI) and anemia of chronic disease (ACD), hemophilia, thrombotic thrombocytopenic purpura (TTP) or VWD type-2B, and sickle cell disease (SCD), in particular, those that have entered into clinical trials.

Keywords: Aptamer, anemia, hemophilia, thrombotic thrombocytopenic purpura, VWD type-2B, sickle cell disease.

Graphical Abstract

[1]
Tuerk, C.; Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science, 1990, 249, 505-510.
[2]
Ellington, A.D.; Szostak, J.W. In vitro selection of RNA molecules that bind specific ligands. Nature, 1990, 346, 818-822.
[3]
Keefe, A.D.; Pai, S.; Ellington, A. Aptamers as therapeutics. Nat. Rev. Drug Discov., 2010, 9, 537-550.
[4]
Dollins, C.M.; Nair, S.; Sullenger, B.A. Aptamers in immunotherapy. Hum. Gene Ther., 2008, 9, 443-450.
[5]
Wu, C.C.; Sabet, M.; Hayashi, T.; Tawatao, R.; Fierer, J.; Carson, D.A.; Guiney, D.G.; Corr, M. In vivo efficacy of a phosphodiester TLR-9 aptamer and its beneficial effect in a pulmonary anthrax infection model. Cell. Immunol., 2008, 251, 78-85.
[6]
Ruckman, J.; Green, L.S.; Beeson, J.; Waugh, S.; Gillette, W.L.; Henninger, D.D.; Claesson-Welsh, L.; Janjić, N. 2′-Fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain. J. Biol. Chem., 1998, 273, 20556-20567.
[7]
Burmeister, P.E.; Lewis, S.D.; Silva, R.F.; Preiss, J.R.; Horwitz, L.R.; Pendergrast, P.S.; McCauley, T.G.; Kurz, J.C.; Epstein, D.M.; Wilson, C.; Keefe, A.D. Direct in vitro selection of a 2′-O-methyl aptamer to VEGF. Chem. Biol., 2005, 12, 25-33.
[8]
Dhar, S.; Gu, F.X.; Langer, R.; Farokhzad, O.C.; Lippard, S.J. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles. Proc. Natl. Acad. Sci. USA, 2008, 105, 17356-17361.
[9]
Bagalkot, V.; Farokhzad, O.C.; Langer, R.; Jon, S. An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. Angew. Chem. Int. Ed. Engl., 2006, 45, 8149-8152.
[10]
Huang, Y.F.; Shangguan, D.; Liu, H.; Phillips, J.A.; Zhang, X.; Chen, Y.; Tan, W. Molecular assembly of an aptamer-drug conjugate for targeted drug delivery to tumor cells. ChemBioChem, 2009, 10, 862-868.
[11]
Diao, Y.; Liu, J.; Ma, Y.; Su, M.; Zhang, H.; Hao, X. A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growth in vivo. Cancer Biol. Ther., 2016, 17, 498-506.
[12]
Yamada, Y.; Furukawa, R.; Harashima, H. A Dual-Ligand liposomal system composed of a cell-penetrating peptide and a mitochondrial rna aptamer synergistically facilitates cellular uptake and mitochondrial targeting. J. Pharm. Sci., 2016, 105, 1705-1713.
[13]
Zhang, J.; Chen, R.; Chen, F.; Chen, M.; Wang, Y. Nucleolin targeting AS1411 aptamer modified pH-sensitive micelles: A dual-functional strategy for paclitaxel delivery. J. Control. Release, 2015, 213, e137-e138.
[14]
Liu, J.; Wei, T.; Zhao, J.; Huang, Y.; Deng, H.; Kumar, A.; Wang, C.; Liang, Z.; Ma, X.; Liang, X.J. Multifunctional aptamer-based nanoparticles for targeted drug delivery to circumvent cancer resistance. Biomaterials, 2016, 91, 44-56.
[15]
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, 123-132.
[16]
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.
[17]
Li, W.; Lan, X. Aptamer Oligonucleotides: Novel potential therapeutic agents in autoimmune disease. Nucleic Acid Ther., 2015, 25, 173-179.
[18]
Steinbicker, A.U. AUID- Oho. A novel treatment of anemia of inflammation. Blood, 2014, 124, 2618-2619.
[19]
Nemeth, E. Anti-hepcidin therapy for iron-restricted anemias. Blood, 2013, 122, 2929-2931.
[20]
Kong, H.Y.; Byun, J. Nucleic Acid aptamers: New methods for selection, stabilization, and application in biomedical science. Biomol. Ther. (Seoul), 2013, 21, 423-434.
[21]
Schwoebel, F.; van Eijk, L.T.; Zboralski, D.; Sell, S.; Buchner, K.; Maasch, C.; Purschke, W.G.; Humphrey, M.; Zöllner, S.; Eulberg, D.; Morich, F.; Pickkers, P.; Klussmann, S. The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood, 2013, 121, 2311-2315.
[22]
Boyce, M.; Warrington, S.; Cortezi, B.; Zöllner, S.; Vauléon, S.; Swinkels, D.W.; Summo, L.; Schwoebel, F.; Riecke, K. Safety, pharmacokinetics and pharmacodynamics of the anti-hepcidin Spiegelmer lexaptepid pegol in healthy subjects. Br. J. Pharmacol., 2016, 173, 1580-1588.
[23]
van Eijk, L.T.; John, A.S.; Schwoebel, F.; Summo, L.; Vauléon, S.; Zöllner, S.; Laarakkers, C.M.; Kox, M.; van der Hoeven, J.G.; Swinkels, D.W.; Riecke, K.; Pickkers, P. Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood, 2014, 124, 2643-2646.
[24]
Georgiev, P. The anti-hepcidin Spiegelmer Lexaptepid Pegol (NOX-H94) as treatment of anemia of chronic disease in patients with multiple myeloma, low grade lymphoma, and CLL: A phase II pilot study. Ann. Meeting Am. Associat. Cancer Res, 2014.
[25]
Pencho Georgiev, M.L.; Luminita Ocroteala, J.G.; Emanuil Gheorghita, M.V. The anti-hepcidin spiegelmer® lexaptepid pegol (noxh94) as treatment of anemia of chronic disease in patients with multiple myeloma, low grade lymphoma, and cll: A phase ii pilot study. the 19th Congress of the European Hematology Association (EHA) in Milan, Italy, 12-15.
[26]
Waters, E.K.; Genga, R.M.; Schwartz, M.C.; Nelson, J.A.; Schaub, R.G.; Olson, K.A.; Kurz, J.C.; McGinness, K.E. Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhibitor. Blood, 2011, 117, 5514-5522.
[27]
Pipe, S. Visions in haemophilia care. Thromb. Res., 2009, 124(Suppl. 2), S2-S5.
[28]
Parunov, L.A.; Fadeeva, O.A.; Balandina, A.N.; Soshitova, N.P.; Kopylov, K.G.; Kumskova, M.A.; Gilbert, J.C.; Schaub, R.G.; McGinness, K.E.; Ataullakhanov, F.I.; Panteleev, M.A. Improvement of spatial fibrin formation by the anti-TFPI aptamer BAX499: Changing clot size by targeting extrinsic pathway initiation. J. Thromb. Haemost., 2011, 9, 1825-1834.
[29]
Gorczyca, M.E.; Nair, S.C.; Jilma, B.; Priya, S.; Male, C.; Reitter, S.; Knoebl, P.; Gilbert, J.C.; Schaub, R.G.; Dockal, M.; McGinness, K.E.; Pabinger, I.; Srivastava, A. Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves clotting of hemophilic blood and plasma. J. Thromb. Haemost., 2012, 10, 1581-1590.
[30]
Chang, J.Y.; Chantrathammachart, P.; Monroe, D.M.; Key, N.S. Studies on the mechanism of action of the aptamer BAX499, an inhibitor of tissue factor pathway inhibitor. Thromb. Res., 2012, 130, e151-e157.
[31]
Gissel, M.; Orfeo, T.; Foley, J.H.; Butenas, S. Effect of BAX499 aptamer on tissue factor pathway inhibitor function and thrombin generation in models of hemophilia. Thromb. Res., 2012, 130, 948-955.
[32]
Waters, E.K.; Genga, R.M.; Thomson, H.A.; Kurz, J.C.; Schaub, R.G.; Scheiflinger, F.; McGinness, K.E. Aptamer BAX 499 mediates inhibition of tissue factor pathway inhibitor via interaction with multiple domains of the protein. J. Thromb. Haemost., 2013, 11, 1137-1145.
[33]
Parunov, L.A.; Soshitova, N.P.; Fadeeva, O.A.; Balandina, A.N.; Kopylov, K.G.; Kumskova, M.A.; Gilbert, J.C.; Schaub, R.G.; McGinness, K.E.; Ataullakhanov, F.I.; Panteleev, M.A. Drug-drug interaction of the anti-TFPI aptamer BAX499 and factor VIII: Studies of spatial dynamics of fibrin clot formation in hemophilia A. Thromb. Res., 2014, 133, 112-119.
[34]
Blombery, P.; Scully, M. Management of thrombotic thrombocytopenic purpura: Current perspectives. J. Blood Med., 2014, 5, 15-23.
[35]
Sadler, J.E. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood, 2008, 112, 11-18.
[36]
Huang, R.H.; Fremont, D.H.; Diener, J.L.; Schaub, R.G.; Sadler, J.E. A structural explanation for the antithrombotic activity of ARC1172, a DNA aptamer that binds von Willebrand factor domain A1. Structure, 2009, 17, 1476-1484.
[37]
Diener, J.L.; Daniel, L.H.A.; Duerschmied, D.; Merhi, Y.; Tanguay, J.F.; Hutabarat, R.; Gilbert, J.; Wagner, D.D.; 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.
[38]
Knobl, P.; Jilma, B.; Gilbert, J.C.; Hutabarat, R.M.; Wagner, P.G.; Jilma-Stohlawetz, P. Anti-von Willebrand factor aptamer ARC1779 for refractory thrombotic thrombocytopenic purpura. Transfus. (Paris), 2009, 49, 2181-2185.
[39]
Mayr, F.B.; Knöbl, P.; Jilma, B.; Siller-Matula, J.M.; Wagner, P.G.; Schaub, R.G.; Gilbert, J.C.; Jilma-Stohlawetz, P. The aptamer ARC1779 blocks von Willebrand factor-dependent platelet function in patients with thrombotic thrombocytopenic purpura ex vivo. Transfusion, 2010, 50, 1079-1087.
[40]
Jilma-Stohlawetz, P.; Gorczyca, M.E.; Jilma, B.; Siller-Matula, J.; Gilbert, J.C.; Knöbl, P. Inhibition of von Willebrand factor by ARC1779 in patients with acute thrombotic thrombocytopenic purpura. Thromb. Haemost., 2011, 105, 545-552.
[41]
Jilma-Stohlawetz, P.; Gilbert, J.C.; Gorczyca, M.E.; Knobl, P.; Jilma, B. A dose ranging phase I/II trial of the von Willebrand factor inhibiting aptamer ARC1779 in patients with congenital thrombotic thrombocytopenic purpura. Thromb. Haemost., 2011, 106, 539-547.
[42]
Cataland, S.R.; Peyvandi, F.; Mannucci, P.M.; Lämmle, B.; Kremer Hovinga, J.A.; Machin, S.J.; Scully, M.; Rock, G.; Gilbert, J.C.; 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.
[43]
Bae, O.N. Targeting von Willebrand factor as a novel anti-platelet therapy; application of ARC1779, an Anti-vWF aptamer, against thrombotic risk. Arch. Pharm. Res., 2012, 35, 1693-1699.
[44]
Sadler, J.E.; Budde, U.; Eikenboom, J.C.; Favaloro, E.J.; Hill, F.G.; Holmberg, L.; Ingerslev, J.; Lee, C.A.; Lillicrap, D.; Mannucci, P.M.; Mazurier, C.; Meyer, D.; Nichols, W.L.; Nishino, M.; Peake, I.R.; Rodeghiero, F.; Schneppenheim, R.; Ruggeri, Z.M.; Srivastava, A.; Montgomery, R.R.; Federici, A.B. Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: A report of the Subcommittee on von Willebrand Factor. J. Thromb. Haemost., 2006, 4, 2103-2114.
[45]
Jilma, B.; Paulinska, P.; Jilma-Stohlawetz, P.; Gilbert, J.C.; Hutabarat, R.; Knobl, P. A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease. Thromb. Haemost., 2010, 104, 563-570.
[46]
Jilma-Stohlawetz, P.; Knobl, P.; Gilbert, J.C.; 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.
[47]
Firbas, C.; Siller-Matula, J.M.; Jilma, B. Targeting von Willebrand factor and platelet glycoprotein Ib receptor. Expert Rev. Cardiovasc. Ther., 2010, 8, 1689-1701.
[48]
Siller-Matula, J.M.; Merhi, Y.; Tanguay, J.F.; Duerschmied, D.; Wagner, D.D.; McGinness, K.E.; Pendergrast, P.S.; Chung, J.K.; Tian, X.; Schaub, R.G.; Jilma, B. ARC15105 is a potent antagonist of von Willebrand factor mediated platelet activation and adhesion. Arterioscler. Thromb. Vasc. Biol., 2012, 32, 902-909.
[49]
Xu, W.; Wang, T.Y.; Becker, R.C. Hematologic diseases: From within the heart. Rev. Esp. Cardiol., 2011, 64, 606-613.
[50]
Fitzhugh, C.D.; Lauder, N.; Jonassaint, J.C.; Telen, M.J.; Zhao, X.; Wright, E.C.; Gilliam, F.R.; De Castro, L.M. Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease. Am. J. Hematol., 2010, 85, 36-40.
[51]
Matsui, N.M.; Borsig, L.; Rosen, S.D.; Yaghmai, M.; Varki, A.; Embury, S.H. P-selectin mediates the adhesion of sickle erythrocytes to the endothelium. Blood, 2001, 98, 1955-1962.
[52]
Jenison, R.D.; Jennings, S.D.; Walker, D.W.; Bargatze, R.F.; Parma, D. Oligonucleotide inhibitors of P-selectin-dependent neutrophil-platelet adhesion. Antisense Nucleic Acid Drug Dev., 1998, 8, 265-279.
[53]
Gutsaeva, D.R.; Parkerson, J.B.; Yerigenahally, S.D.; Kurz, J.C.; Schaub, R.G.; Ikuta, T.; Head, C.A. Inhibition of cell adhesion by anti-P-selectin aptamer: A new potential therapeutic agent for sickle cell disease. Blood, 2011, 117, 727-735.
[54]
Mi, J.; Zhang, X.; Giangrande, P.H.; McNamara, J.O. 2nd; Nimjee, S.M.; Sarraf-Yazdi, S.; Sullenger, B.A.; Clary, B.M. Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival. Biochem. Biophys. Res. Commun., 2005, 338, 956-963.
[55]
Zennadi, R.; Hines, P.C.; De Castro, L.M.; Cartron, J.P.; Parise, L.V.; Telen, M.J. Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood, 2004, 104, 3774-3781.
[56]
Burnette, A.D.; Nimjee, S.M.; Batchvarova, M.; Zennadi, R.; Telen, M.J.; Nishimura, J.; Sullenger, B.A. RNA aptamer therapy for vaso-occlusion in sickle cell disease. Nucleic Acid Ther., 2011, 21, 275-283.
[57]
Faryammanesh, R.; Lange, T.; Magbanua, E.; Haas, S.; Meyer, C.; Wicklein, D.; Schumacher, U.; Hahn, U. SDA, a DNA aptamer inhibiting E- and P-selectin mediated adhesion of cancer and leukemia cells, the first and pivotal step in transendothelial migration during metastasis formation. PLoS One, 2014, 9e93173

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