Abstract
Aptamers are short oligonucleotides or peptides capable of targeting the various molecules with higher specificity and better affinity. However, aptamers are natural in origin, but at laboratory level, they can be synthesized artificially from large random sequence pools. These exhibit promising advantages in terms of their size, synthetic approach and alteration by suitable methodology. As compared to antibodies, aptamers seems to be significant alternatives in various therapeutic applications. In 1990, a robust aptamer screening method was developed known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). It became a powerful diagnostic and therapeutic research tool in this newly emerging field. In addition, aptamers have proved themselves to be a powerful tool in delivering a variety of therapeutic agents like small molecular drugs, peptides and specially RNA based therapeutics into specific cells to cure different human diseases. Aptamers have attracted various research groups to be used as important candidate molecule in cancer therapies.
In this chapter, authors have attempted to compile and present the various applications and problems hindering the widespread use of aptamers in therapeutic field, besides the new approaches that might be exploited to expand and improve the range of aptamer applications in medical sciences.
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References
Adley CC (2014) Past, present and future of sensors in food production. Foods 3(3):491–510
Amaya-González S, de-los-Santos-Álvarez N, Miranda-Ordieres AJ, Lobo-Castañón MJ (2013) Aptamer-based analysis: a promising alternative for food safety control. Sensors 13(12):16292–16311
Arnau J, Lauritzen C, Petersen GE, Pedersen J (2006) Current strategies for the use of affinity tags and tag removal for the purification of recombinant proteins. Protein Expr Purif 48(1):1–13
Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S (2001) Botulinum toxin as a biological weapon: medical and public health management. JAMA 285(8):1059–1070
Ausländer D, Wieland M, Ausländer S, Tigges M, Fussenegger M (2011) Rational design of a small molecule-responsive intramer controlling transgene expression in mammalian cells. Nucleic Acids Res 39(22):e155–e155
Bompiani KM, Monroe DM, Church FC, Sullenger BA (2012a) A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity. J Thromb Haemost 10(5):870–880
Bompiani KM, Woodruff RS, Becker RC, Nimjee SM, Sullenger BA (2012b) Antidote control of aptamer therapeutics: the road to a safer class of drug agents. Curr Pharm Biotechnol 13(10):1924–1934
Bouchard PR, Hutabarat RM, Thompson KM (2010) Discovery and development of therapeutic aptamers. Annu Rev Pharmacol Toxicol 50:237–257
Brieke C, Rohrbach F, Gottschalk A, Mayer G, Heckel A (2012) Light-controlled tools. Angew Chem Int Ed 51(34):8446–8476
Brody EN, Gold L (2000) Aptamers as therapeutic and diagnostic agents. Rev Mol Biotechnol 74(1):5–13
Buff MC, Schäfer F, Wulffen B, Müller J, Pötzsch B, Heckel A, Mayer G (2009) Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency. Nucleic Acids Res 38(6):2111–2118
Bunka DH, Stockley PG (2006) Aptamers come of age–at last. Nat Rev Microbiol 4(8):588–596
Burmeister PE, Lewis SD, Silva RF, Preiss JR, Horwitz LR, Pendergrast PS, McCauley TG, Kurz JC, Epstein DM, Wilson C, Keefe AD (2005) Direct in vitro selection of a 20 -O-methyl aptamer to VEGF. Chem Biol 12:25–33
Chaloin L, Lehmann MJ, Sczakiel G, Restle T (2002) Endogenous expression of a high-affinity pseudoknot RNA aptamer suppresses replication of HIV-1. Nucleic Acids Res 30(18):4001–4008
Chang TW, Blank M, Janardhanan P, Singh BR, Mello C, Blind M, Cai S (2010) In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin. Biochem Biophys Res Commun 396(4):854–860
Ciesiolka J, Gorski J, Yarus M (1995) Selection of an RNA domain that binds Zn2+. RNA 1(5):538–550
Coiffier B, Lepage E, Herbrecht R, Tilly H, Solal-Celigny P, Munck JN, Bouabdallah R, Lederlin P, Sebban C, Morel P, Haioun C (2000) Mab Thera (rituximab) plus CHOP is superior to CHOP alone in elderly patients with diffuse large B-cell lymphoma (DLCL): interim results of a randomized GELA trial. Blood 96(11):223A–223A
Cox JC, Ellington AD (2001) Automated selection of anti-protein aptamers. Bioorg Med Chem 9(10):2525–2531
Davydova AS, Vorobjeva MA, Venyaminova AG (2011) Escort aptamers: new tools for the targeteddelivery of therapeutics into cells. Acta Naturae (англоязычная версия) 34(11):12–29
Derbyshire N, White SJ, Bunka DH, Song L, Stead S, Tarbin J, Sharman M, Zhou D, Stockley PG (2012) Toggled RNA aptamers against aminoglycosides allowing facile detection of antibiotics using gold nanoparticle assays. Anal Chem 84(15):6595–6602
Dudak FC, Boyaci İH (2014) Peptide-based surface plasmon resonance biosensor for detection of staphylococcal enterotoxin b. Food Anal Methods 7(2):506–511
Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346(6287):818–822
Eulberg D, Klussmann S (2003) Spiegelmers: biostable aptamers. Chembiochem 4(10):979–983
Eulberg D, Buchner K, Maasch C, Klussmann S (2005) Development of an automated in vitro selection protocol to obtain RNA-based aptamers: identification of a biostable substance P antagonist. Nucleic Acids Res 33(4):e45–e45
Famulok M, Hartig JS, Mayer G (2007) Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem Rev 107(9):3715–3743
Gold L (1995) Oligonucleotides as research, diagnostic, and therapeutic agents. J Biol Chem 270(23):13581–13584
Good PD, Krikos AJ, Li SXL, Bertrand E, Lee NS, Giver L, Ellington A, Zaia JA, Rossi JJ, Engelke DR (1997) Expression of small, therapeutic RNAs in human cell nuclei. Gene Ther 4(1):45–54
Gray BP, Kelly L, Levy M, Sullenger BA (2015) 65. A novel aptamer targeting agent for prostate Cancer. Mol Ther 23:S28–S29
Hafner M, Vianini E, Albertoni B, Marchetti L, Grüne I, Gloeckner C, Famulok M (2008) Displacement of protein-bound aptamers with small molecules screened by fluorescence polarization. Nat Protoc 3(4):579–587
Hall TC, Choi OS, Abadi A, Krant MJ (1967) High-dose corticoid therapy in Hodgkin’s disease and other lymphomas. Ann Intern Med 66(6):1144–1153
Han B, Zhao C, Yin J, Wang H (2012) High performance aptamer affinity chromatography for single-step selective extraction and screening of basic protein lysozyme. J Chromatogr B 903:112–117
Healy JM, Lewis SD, Kurz M, Boomer RM, Thompson KM, Wilson C, McCauley TG (2004) Pharmacokinetics and biodistribution of novel aptamer compositions. Pharm Res 21(12):2234–2246
Hernandez FJ, Stockdale KR, Huang L, Horswill AR, Behlke MA, McNamara JO (2012) Degradation of nuclease-stabilized RNA oligonucleotides in mycoplasma-contaminated cell culture media. Nucleic Acid Ther 22(1):58–68
Hicke BJ, Marion C, Chang YF, Gould T, Lynott CK, Parma D, Schmidt PG, Warren S (2001) Tenascin-C aptamers are generated using tumor cells and purified protein. J Biol Chem 276(52):48644–48654
Huang L, Reekmans G, Saerens D, Friedt JM, Frederix F, Francis L, Muyldermans S, Campitelli A, Van Hoof C (2005) Prostate-specific antigen immunosensing based on mixed self-assembled monolayers, camel antibodies and colloidal gold enhanced sandwich assays. Biosens Bioelectron 21(3):483–490
Hwang KS, Lee JH, Park J, Yoon DS, Park JH, Kim TS (2004) In-situ quantitative analysis of a prostate-specific antigen (PSA) using a nanomechanical PZT cantilever. Lab Chip 4(6):547–552
Javaherian S, Musheev MU, Kanoatov M, Berezovski MV, Krylov SN (2009) Selection of aptamers for a protein target in cell lysate and their application to protein purification. Nucleic Acids Res 37(8):e62–e62
Jayasena SD (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 45(9):1628–1650
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90
Jo H, Ban C (2016) Aptamer–nanoparticle complexes as powerful diagnostic and therapeutic tools. Exp Mol Med 48(5):e230
Kanoatov M, Javaherian S, Krylov SN (2010) Selection of aptamers for a non-DNA binding protein in the context of cell lysate. Anal Chim Acta 681(1–2):92–97
Katz E, Willner I (2003) Probing biomolecular interactions at conductive and semiconductive surfaces by impedance spectroscopy: routes to impedimetric immunosensors, DNA-sensors, and enzyme biosensors. Electroanalysis 15(11):913–947
Kuwahara M, Sugimoto N (2010) Molecular evolution of functional nucleic acids with chemical modifications. Molecules 15(8):5423–5444
Lakhin AV, Tarantul VZ, Gening LV (2013) Aptamers: problems, solutions and prospects. Acta Naturae (англоязычная версия) 5(4):34–43
Lao YH, Phua KK, Leong KW (2015) Aptamer nanomedicine for cancer therapeutics: barriers and potential for translation. ACS Nano 9(3):2235–2254
Lebars I, Richard T, Di Primo C, Toulmé JJ (2007) LNA derivatives of a kissing aptamer targeted to the trans-activating responsive RNA element of HIV-1. Blood Cell Mol Dis 38(3):204–209
Lee JW, Kim HJ, Heo K (2015) Therapeutic aptamers: developmental potential as anticancer drugs. BMB Rep 48(4):234–237
Levay A, Brenneman R, Hoinka J, Sant D, Cardone M, Trinchieri G, Przytycka TM, Berezhnoy A (2015) Identifying high-affinity aptamer ligands with defined cross-reactivity using high-throughput guided systematic evolution of ligands by exponential enrichment. Nucleic Acids Res 43(12):e82–e82
Li S, Xu H, Ding H, Huang Y, Cao X, Yang G, Li J, Xie Z, Meng Y, Li X, Zhao Q (2009) Identification of an aptamer targeting hnRNP A1 by tissue slide-based SELEX. J Pathol 218(3):327–336
Liu J, Cao Z, Lu Y (2009) Functional nucleic acid sensors. Chem Rev 109(5):1948–1998
Liu Z, Duan JH, Song YM, Ma J, Wang FD, Lu X, Yang XD (2012) Novel HER2 aptamer selectively delivers cytotoxic drug to HER2-positive breast cancer cells in vitro. J Transl Med 10(1):148
Mascini M (2008) Aptamers and their applications. Anal Bioanal Chem 390(4):987–988
Mascini M, Palchetti I, Tombelli S (2012) Nucleic acid and peptide aptamers: fundamentals and bioanalytical aspects. Angew Chem Int Ed 51(6):1316–1332
Mayer G (2009) The chemical biology of aptamers. Angew Chem Int Ed 48(15):2672–2689
Menne J, Eulberg D, Beyer D, Baumann M, Saudek F, Valkusz Z, Wiecek A, Haller H, Emapticap Study Group (2016) CC motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria. Nephrol Dial Transplant 32(2):307–315
Meyer C, Eydeler K, Magbanua E, Zivkovic T, Piganeau N, Lorenzen I, Grötzinger J, Mayer G, Rose-John S, Hahn U (2012) Interleukin-6 receptor specific RNA aptamers for cargo delivery into target cells. RNA Biol 9(1):67–80
Mi J, Liu Y, Rabbani ZN, Yang Z, Urban JH, Sullenger BA, Clary BM (2010) In vivo selection of tumor-targeting RNA motifs. Nat Chem Biol 6(1):22–24
Milla P, Dosio F, Cattel L (2012) PEGylation of proteins and liposomes: a powerful and flexible strategy to improve the drug delivery. Curr Drug Metab 13(1):105–119
Ng EW, Shima DT, Calias P, Cunningham ET Jr, Guyer DR, Adamis AP (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 5(2):123–132
Ni X, Castanares M, Mukherjee A, Lupold SE (2011) Nucleic acid aptamers: clinical applications and promising new horizons. Curr Med Chem 18(27):4206–4214
Nitsche A, Kurth A, Dunkhorst A, Pänke O, Sielaff H, Junge W, Muth D, Scheller F, Stöcklein W, Dahmen C, Pauli G (2007) One-step selection of vaccinia virus-binding DNA aptamers by mono LEX. BMC Biotechnol 7(1):48
Oney S, Lam RT, Bompiani KM, Blake CM, Quick G, Heidel JD, Liu JYC, Mack BC, Davis ME, Leong KW, Sullenger BA (2009) Development of universal antidotes to control aptamer activity. Nat Med 15(10):1224–1228
Ozalp VC, Eyidogan F, Oktem HA (2011) Aptamer-gated nanoparticles for smart drug delivery. Pharmaceuticals 4(8):1137–1157
Parashar A (2016) Aptamers in therapeutics. J Clin Diagn Res 10(6):BE01–BE06
Pasut G, Veronese FM (2012) State of the art in PEGylation: the great versatility achieved after forty years of research. J Control Release 161(2):461–472
Pratico ED, Nair SK, Sullenger BA (2015) 66. Identification and characterization of a B cell aptamer that targets diffuse large B cell lymphoma (DLBCL) and chronic myelogenous leukemia (CML). Mol Ther 23:S29
Proske D, Blank M, Buhmann R, Resch A (2005) Aptamers—basic research, drug development, and clinical applications. Appl Microbiol Biotechnol 69(4):367–374
Ruckman J, Green LS, Beeson J, Waugh S, Gillette WL, Henninger DD, Claesson-Welsh L, Janjic N (1998) 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 273(32):20556–20567
Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA (2002) RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 419(6902):90–94
Scheinberg DA, Villa CH, Escorcia FE, McDevitt MR (2010) Conscripts of the infinite armada: systemic cancer therapy using nanomaterials. Nat Rev Clin Oncol 7(5):266–276
Shangguan D, Li Y, Tang Z, Cao ZC, Chen HW, Mallikaratchy P, Sefah K, Yang CJ, Tan W (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci 103(32):11838–11843
Sheng W, Chen T, Kamath R, Xiong X, Tan W, Fan ZH (2012) Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device. Anal Chem 84(9):4199–4206
Shigdar S, Macdonald J, O’Connor M, Wang T, Xiang D, Al Shamaileh H, Qiao L, Wei M, Zhou SF, Zhu Y, Kong L (2013) Aptamers as theranostic agents: modifications, serum stability and functionalisation. Sensors 13(10):13624–13637
Shum KT, Zhou J, Rossi JJ (2013) Aptamer-based therapeutics: new approaches to combat human viral diseases. Pharmaceuticals 6(12):1507–1542
Song KM, Lee S, Ban C (2012) Aptamers and their biological applications. Sensors 12(1):612–631
Stoltenburg R, Nikolaus N, Strehlitz B Capture-SELEX: selection of DNA aptamers for aminoglycoside antibiotics. J Anal Methods Chem 2012:1–14
Sun H, Zu Y (2015) A highlight of recent advances in aptamer technology and its application. Molecules 20(7):11959–11980
Sun H et al (2014) Oligonucleotide aptamers: new tools for targeted cancer therapy. Mol Ther Nucleic Acids 3:e182
Thielemans K, Maloney DG, Meeker T, Fujimoto J, Doss C, Warnke RA, Bindl J, Gralow J, Miller RA, Levy R (1984) Strategies for production of monoclonal anti-idiotype antibodies against human B cell lymphomas. J Immunol 133(1):495–501
Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510
Turner JJ, Hoos JS, Vonhoff S, Klussmann S (2011) Methods for L-ribooligonucleotide sequence determination using LCMS. Nucleic Acids Res 39(21):e147–e147
Wan Y, Liu Y, Allen PB, Asghar W, Mahmood MAI, Tan J, Duhon H, Kim YT, Ellington AD, Iqbal SM (2012) Capture, isolation and release of cancer cells with aptamer-functionalized glass bead array. Lab Chip 12(22):4693–4701
Wandtke T, Woźniak J, Kopiński P (2015) Aptamers in diagnostics and treatment of viral infections. Viruses 7(2):751–780
Wilson DS, Szostak JW (1999) In vitro selection of functional nucleic acids. Annu Rev Biochem 68(1):611–647
Xiang D, Shigdar S, Qiao G, Wang T, Kouzani AZ, Zhou SF, Kong L, Li Y, Pu C, Duan W (2015) Nucleic acid aptamer-guided cancer therapeutics and diagnostics: the next generation of cancer medicine. Theranostics 5(1):23–42
Yamazaki S, Tan L, Mayer G, Hartig JS, Song JN, Reuter S, Restle T, Laufer SD, Grohmann D, Kräusslich HG, Bajorath J (2007) Aptamer displacement identifies alternative small-molecule target sites that escape viral resistance. Chem Biol 14(7):804–812
Yan X, Gao X, Zhang Z (2004) Isolation and characterization of 2′-amino-modified RNA aptamers for human TNFα. Genomics Proteomics Bioinf 2(1):32–42
Yang Q, Goldstein IJ, Mei HY, Engelke DR (1998) DNA ligands that bind tightly and selectively to cellobiose. Proc Natl Acad Sci 95(10):5462–5467
Yang J, Kim SE, Cho M, Yoo IK, Choe WS, Lee Y (2014) Highly sensitive and selective determination of bisphenol-A using peptide-modified gold electrode. Biosens Bioelectron 61:38–44
Ye M, Hu J, Peng M, Liu J, Liu J, Liu H, Zhao X, Tan W (2012) Generating aptamers by cell-SELEX for applications in molecular medicine. Int J Mol Sci 13(3):3341–3353
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Singhal, P. et al. (2019). Aptamers: Novel Therapeutic and Diagnostic Molecules. In: Yadav, G., Kumar, V., Aggarwal, N. (eds) Aptamers. Springer, Singapore. https://doi.org/10.1007/978-981-13-8836-1_5
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