Journal of Molecular Medicine

, Volume 91, Issue 12, pp 1333–1342

Aptamers: multifunctional molecules for biomedical research

Review

Abstract

Aptamers are single-stranded oligonucleotides that fold into well-defined three-dimensional shapes, allowing them to bind their targets with high affinity and specificity. They can be generated through an in vitro process called “Systemic Evolution of Ligands by Exponential Enrichment” and applied for specific detection, inhibition, and characterization of various targets like small organic and inorganic molecules, proteins, and whole cells. Aptamers have also been called chemical antibodies because of their synthetic origin and their similar modes of action to antibodies. They exhibit significant advantages over antibodies in terms of their small size, synthetic accessibility, and ability to be chemically modified and thus endowed with new properties. The first generation of aptamer drug “Macugen” was available for public use within 25 years of the discovery of aptamers. With others in the pipeline for clinical trials, this emerging field of medical biotechnology is raising significant interest. However, aptamers pose different problems for their development than for antibodies that need to be addressed to achieve practical applications. It is likely that current developments in aptamer engineering will be the basis for the evolution of improved future bioanalytical and biomedical applications. The present review discusses the development of aptamers for therapeutics, drug delivery, target validation and imaging, and reviews some of the challenges to fully realizing the promise of aptamers in biomedical applications.

Keywords

Aptamer Biosensors Drug delivery In vitro selection Modified nucleic acid SELEX 

References

  1. 1.
    Hermann T, Patel DJ (2000) Adaptive recognition by nucleic acid aptamers. Science 287:820–825PubMedGoogle Scholar
  2. 2.
    Zhang Q, Sun X, Watt ED, Al-Hashimi HM (2006) Resolving the motional modes that code for RNA adaptation. Science 311:653–656PubMedGoogle Scholar
  3. 3.
    Zhang Q, Stelzer AC, Fisher CK, Al-Hashimi HM (2007) Visualizing spatially correlated dynamics that directs RNA conformational transitions. Nature 450:1263–1267PubMedGoogle Scholar
  4. 4.
    Duchardt-Ferner E, Weigand JE, Ohlenschlager O, Schmidtke SR, Suess B, Wohnert J (2010) Highly modular structure and ligand binding by conformational capture in a minimalistic riboswitch. Angew Chem Int Ed Engl 49:6216–6219PubMedGoogle Scholar
  5. 5.
    Wunnicke D, Strohbach D, Weigand JE, Appel B, Feresin E, Suess B, Muller S, Steinhoff HJ (2011) Ligand-induced conformational capture of a synthetic tetracycline riboswitch revealed by pulse EPR. RNA 17:182–188PubMedGoogle Scholar
  6. 6.
    Chen B, Zuo X, Wang YX, Dayie TK (2012) Multiple conformations of SAM-II riboswitch detected with SAXS and NMR spectroscopy. Nucleic Acids Res 40:3117–3130PubMedGoogle Scholar
  7. 7.
    Banerjee J (2010) Antibodies are challenged. Indian J Med Sci 64:144–147PubMedGoogle Scholar
  8. 8.
    Jayasena S (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 45:1628–1650PubMedGoogle Scholar
  9. 9.
    Lo AS, Zhu Q, Marasco WA (2008) Intracellular antibodies (intrabodies) and their therapeutic potential. Handb Exp Pharmacol 181:343–373PubMedGoogle Scholar
  10. 10.
    Que-Gewirth NS, Sullenger BA (2007) Gene therapy progress and prospects: RNA aptamers. Gene Ther 14:283–291PubMedGoogle Scholar
  11. 11.
    Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822PubMedGoogle Scholar
  12. 12.
    Robertson DL, Joyce GF (1990) Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344:467–468PubMedGoogle Scholar
  13. 13.
    Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510PubMedGoogle Scholar
  14. 14.
    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 6:22–24PubMedGoogle Scholar
  15. 15.
    Cheng C, Chen Y, Lennox K, Behlke M, Davidson BL (2013) In vivo SELEX for identification of brain-penetrating aptamers. Mol Ther Nucleic Acids 2:e67. doi:10.1038/mt.2012.59 PubMedGoogle Scholar
  16. 16.
    Cox JC, Ellington AD (2001) Automated selection of anti-protein aptamers. Bioorg Med Chem 9:2525–2531PubMedGoogle Scholar
  17. 17.
    Lee JF, Stovall GM, Ellington AD (2006) Aptamer therapeutics advance. Curr Opin Chem Biol 10:282–289PubMedGoogle Scholar
  18. 18.
    Kusser W (2000) Chemically modified nucleic acid aptamers for in vitro selections: evolving evolution. J Biotechnol 74:27–38PubMedGoogle Scholar
  19. 19.
    Foy JW, Rittenhouse K, Modi M, Patel M (2007) Local tolerance and systemic safety of pegaptanib sodium in the dog and rabbit. J Ocul Pharmacol Ther 23:452–466PubMedGoogle Scholar
  20. 20.
    Yu D, Wang D, Zhu FG, Bhagat L, Dai M, Kandimalla ER, Agrawal S (2009) Modifications incorporated in CpG motifs of oligodeoxynucleotides lead to antagonist activity of toll-like receptors 7 and 9. J Med Chem 52:5108–5114PubMedGoogle Scholar
  21. 21.
    Ng EW, Adamis AP (2006) Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases. Ann N Y Acad Sci 1082:151–171PubMedGoogle Scholar
  22. 22.
    Gold L, Janjic N, Jarvis T, Schneider D, Walker JJ, Wilcox SK, Zichi D (2012) Aptamers and the RNA world, past and present. Cold Spring Harb Perspect Biol 4:a003582PubMedGoogle Scholar
  23. 23.
    Sundaram P, Kurniawan H, Byrne M, Wower J (2013) Therapeutic RNA aptamers in clinical trials. Eur J Pharm Sci 48:259–271PubMedGoogle Scholar
  24. 24.
    DeAnda A Jr, Coutre SE, Moon MR, Vial CM, Griffin LC, Law VS, Komeda M, Leung LL, Miller DC (1994) Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass. Ann Thorac Surg 58:344–350PubMedGoogle Scholar
  25. 25.
    Rusconi CP, Roberts JD, Pitoc GA, Nimjee SM, White RR, Quick G Jr, Scardino E, Fay WP, Sullenger BA (2004) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnol 22:1423–1428PubMedGoogle Scholar
  26. 26.
    Blind M, Kolanus W, Famulok M (1999) Cytoplasmic RNA modulators of an inside-out signal-transduction cascade. PNAS 96:3606–3610PubMedGoogle Scholar
  27. 27.
    DeStefano JJ, Nair GR (2008) Novel aptamer inhibitors of human immunodeficiency virus reverse transcriptase. Oligonucleotides 18:133–144PubMedGoogle Scholar
  28. 28.
    Li N, Wang Y, Pothukuchy A, Syrett A, Husain N, Gopalakrisha S, Kosaraju P, Ellington AD (2008) Aptamers that recognize drug-resistant HIV-1 reverse transcriptase. Nucleic Acids Res 36:6739–6751PubMedGoogle Scholar
  29. 29.
    Michalowski D, Chitima-Matsiga R, Held DM, Burke DH (2008) Novel bimodular DNA aptamers with guanosine quadruplexes inhibit phylogenetically diverse HIV-1 reverse transcriptases. Nucleic Acids Res 36:7124–7135PubMedGoogle Scholar
  30. 30.
    Ditzler MA, Bose D, Shkriabai N, Marchand B, Sarafianos SG, Kvaratskhelia M, Burke DH (2011) Broad-spectrum aptamer inhibitors of HIV reverse transcriptase closely mimic natural substrates. Nucleic Acids Res 39:8237–8247PubMedGoogle Scholar
  31. 31.
    Symensma TL, Giver L, Zapp M, Takle GB, Ellington AD (1996) RNA aptamers selected to bind human immunodeficiency virus type 1 Rev in vitro are Rev responsive in vivo. J Virol 70:179–187PubMedGoogle Scholar
  32. 32.
    Yamamoto R, Toyoda S, Viljanen P, Machida K, Nishikawa S, Murakami K, Taira K, Kumar PK (1995) In vitro selection of RNA aptamers that can bind specifically to Tat protein of HIV-1. Nucleic Acids Symp Ser 34:145–146PubMedGoogle Scholar
  33. 33.
    Allen P, Worland S, Gold L (1995) Isolation of high-affinity RNA ligands to HIV-1 integrase from a random pool. Virology 209:327–336PubMedGoogle Scholar
  34. 34.
    Kohn DB, Bauer G, Rice CR, Rothschild JC, Carbonaro DA, Valdez P, Q-l H, Zhou C, Bahner I, Kearns K et al (1999) A Clinical trial of retroviral-mediated transfer of arev-responsive element decoy gene into CD34 + Cells from the bone marrow of human immunodeficiency virus-1-infected children. Blood 94:368–371PubMedGoogle Scholar
  35. 35.
    Dey AK, Khati M, Tang M, Wyatt R, Lea SM, James W (2005) An aptamer that neutralizes R5 strains of human immunodeficiency virus type 1 blocks gp120-CCR5 interaction. J Virol 79:13806–13810PubMedGoogle Scholar
  36. 36.
    Cohen C, Forzan M, Sproat B, Pantophlet R, McGowan I, Burton D, James W (2008) An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site. Virology 381:46–54PubMedGoogle Scholar
  37. 37.
    Mufhandu HT, Gray ES, Madiga MC, Tumba N, Alexandre KB, Khoza T, Wibmer CK, Moore PL, Morris L, Khati M (2012) UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C. J Virol 86:4989–4999PubMedGoogle Scholar
  38. 38.
    Neff CP, Zhou J, Remling L, Kuruvilla J, Zhang J, Li H, Smith DD, Swiderski P, Rossi JJ, Akkina R (2011) An aptamer-siRNA chimera suppresses HIV-1 viral loads and protects from helper CD4(+) T cell decline in humanized mice. Sci Transl Med 3:66ra66. doi:10.1126/scitranslmed.3001581 Google Scholar
  39. 39.
    Binning J, Leung D, Amarasinghe G (2012) Aptamers in virology: recent advances and challenges. Front Microbiol 3:29PubMedGoogle Scholar
  40. 40.
    Adler A, Forster N, Homann M, Goringer HU (2008) Post-SELEX chemical optimization of a trypanosome-specific RNA aptamer. Comb Chem High Throughput Screen 11:16–23PubMedGoogle Scholar
  41. 41.
    Barfod A, Persson T, Lindh J (2009) In vitro selection of RNA aptamers against a conserved region of the Plasmodium falciparum erythrocyte membrane protein 1. Parasitol Res 105:1557–1566PubMedGoogle Scholar
  42. 42.
    Chen F, Zhang X, Zhou J, Liu S, Liu J (2012) Aptamer inhibits Mycobacterium tuberculosis (H37Rv) invasion of macrophage. Mol Biol Rep 39:2157–2162PubMedGoogle Scholar
  43. 43.
    Li H, Ding X, Peng Z, Deng L, Wang D, Chen H, He Q (2011) Aptamer selection for the detection of Escherichia coli K88. Can J Microbiol 57:453–459PubMedGoogle Scholar
  44. 44.
    Torres-Chavolla E, Alocilja EC (2009) Aptasensors for detection of microbial and viral pathogens. Biosens Bioelectron 24:3175–3182PubMedGoogle Scholar
  45. 45.
    Sefah K, Tang Z, Shangguan D, Chen H, Lopez-Colon D, Li Y, Parekh P, Martin J, Meng L, Phillips J et al (2009) Molecular recognition of acute myeloid leukemia using aptamers. Leukemia 23:235–244PubMedGoogle Scholar
  46. 46.
    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 13:3341–3353PubMedGoogle Scholar
  47. 47.
    Graham J, Zarbl H (2012) Use of cell-SELEX to generate DNA aptamers as molecular probes of HPV-associated cervical cancer cells. PLoS ONE 7:e36103PubMedGoogle Scholar
  48. 48.
    Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO (2009) Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp Mol Pathol 86:151–164PubMedGoogle Scholar
  49. 49.
    Soundararajan S, Chen W, Spicer EK, Courtenay-Luck N, Fernandes DJ (2008) The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer Res 68:2358–2365PubMedGoogle Scholar
  50. 50.
    Reyes-Reyes EM, Teng Y, Bates PJ (2010) A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism. Cancer Res 70:8617–8629PubMedGoogle Scholar
  51. 51.
    Mi Z, Guo H, Russell MB, Liu Y, Sullenger BA, Kuo PC (2009) RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells. Mol Ther 17:153–161PubMedGoogle Scholar
  52. 52.
    Blake CM, Sullenger BA, Lawrence DA, Fortenberry YM (2009) Antimetastatic potential of PAI-1-specific RNA aptamers. Oligonucleotides 19:117–128PubMedGoogle Scholar
  53. 53.
    Liu Y, Kuan CT, Mi J, Zhang X, Clary BM, Bigner DD, Sullenger BA (2009) Aptamers selected against the unglycosylated EGFRvIII ectodomain and delivered intracellularly reduce membrane-bound EGFRvIII and induce apoptosis. Biol Chem 390:137–144PubMedGoogle Scholar
  54. 54.
    Ferreira CS, Cheung MC, Missailidis S, Bisland S, Gariepy J (2009) Phototoxic aptamers selectively enter and kill epithelial cancer cells. Nucleic Acids Res 37:866–876PubMedGoogle Scholar
  55. 55.
    Heldin CH, Rubin K, Pietras K, Ostman A (2004) High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer 4:806–813PubMedGoogle Scholar
  56. 56.
    Pendergrast PS, Marsh HN, Grate D, Healy JM, Stanton M (2005) Nucleic acid aptamers for target validation and therapeutic applications. J Biomol Tech 16:224–234PubMedGoogle Scholar
  57. 57.
    Takemura K, Wang P, Vorberg I, Surewicz W, Priola SA, Kanthasamy A, Pottathil R, Chen SG, Sreevatsan S (2006) DNA aptamers that bind to PrP(C) and not PrP(Sc) show sequence and structure specificity. Exp Biol Med (Maywood) 231:204–214Google Scholar
  58. 58.
    Gilch S, Schatzl HM (2009) Aptamers against prion proteins and prions. Cell Mol Life Sci 66:2445–2455PubMedGoogle Scholar
  59. 59.
    Hwang B, Han K, Lee SW (2003) Prevention of passively transferred experimental autoimmune myasthenia gravis by an in vitro selected RNA aptamer. FEBS Lett 548:85–89PubMedGoogle Scholar
  60. 60.
    Gutsaeva DR, Parkerson JB, Yerigenahally SD, Kurz JC, Schaub RG, Ikuta T, Head CA (2011) Inhibition of cell adhesion by anti-P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood 117:727–735PubMedGoogle Scholar
  61. 61.
    Haile LA, von Wasielewski R, Gamrekelashvili J, Krüger C, Bachmann O, Westendorf AM, Buer J, Liblau R, Manns MP, Korangy F et al (2008) Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology 135:871–881. doi:10.1053/j.gastro.2008.06.032, e5PubMedGoogle Scholar
  62. 62.
    Waldron T, Quatromoni J, Karakasheva T, Singhal S, Rustgi A (2013) Myeloid-derived suppressor cells: targets for therapy. Oncol Immunol 2:e24117Google Scholar
  63. 63.
    Roth F, De La Fuente AC, Vella JL, Zoso A, Inverardi L, Serafini P (2012) Aptamer-mediated blockade of IL4Rα triggers apoptosis of MDSCs and limits tumor progression. Cancer Res 72(6):1373–1383PubMedGoogle Scholar
  64. 64.
    Ray P, White R (2010) Aptamers for targeted drug delivery. Pharmaceuticals 3:1761–1778Google Scholar
  65. 65.
    Meyer C, Hahn U, Rentmeister A (2011) Cell-specific aptamers as emerging therapeutics. J Nucleic Acids 2011:904750PubMedGoogle Scholar
  66. 66.
    Bagalkot V, Zhang L, Levy-Nissenbaum E, Jon S, Kantoff PW, Langer R, Farokhzad OC (2007) Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. Nano Lett 7:3065–3070PubMedGoogle Scholar
  67. 67.
    Zhang L, Radovic-Moreno AF, Alexis F, Gu FX, Basto PA, Bagalkot V, Jon S, Langer RS, Farokhzad OC (2007) Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle-aptamer bioconjugates. Chem Med Chem 2:1268–1271PubMedGoogle Scholar
  68. 68.
    Xiao Z, Shangguan D, Cao Z, Fang X, Tan W (2008) Cell-specific internalization study of an aptamer from whole cell selection. Chemistry 14:1769–1775PubMedGoogle Scholar
  69. 69.
    McNamara JO 2nd, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH (2006) Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 24:1005–1015PubMedGoogle Scholar
  70. 70.
    Dassie JP, Liu XY, Thomas GS, Whitaker RM, Thiel KW, Stockdale KR, Meyerholz DK, McCaffrey AP, McNamara JO 2nd, Giangrande PH (2009) Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol 27:839–849PubMedGoogle Scholar
  71. 71.
    Chu TC, Twu KY, Ellington AD, Levy M (2006) Aptamer mediated siRNA delivery. Nucleic Acids Res 34:e73PubMedGoogle Scholar
  72. 72.
    Wullner U, Neef I, Eller A, Kleines M, Tur MK, Barth S (2008) Cell-specific induction of apoptosis by rationally designed bivalent aptamer-siRNA transcripts silencing eukaryotic elongation factor 2. Curr Cancer Drug Targets 8:554–565PubMedGoogle Scholar
  73. 73.
    Chu TC, Marks JW 3rd, Lavery LA, Faulkner S, Rosenblum MG, Ellington AD, Levy M (2006) Aptamer: toxin conjugates that specifically target prostate tumor cells. Cancer Res 66:5989–5992PubMedGoogle Scholar
  74. 74.
    Zhang K, Sefah K, Tang L, Zhao Z, Zhu G, Ye M, Sun W, Goodison S, Tan W (2012) A novel aptamer developed for breast cancer cell internalization. Chem Med Chem 7:79–84PubMedGoogle Scholar
  75. 75.
    Chen CH, Dellamaggiore KR, Ouellette CP, Sedano CD, Lizadjohry M, Chernis GA, Gonzales M, Baltasar FE, Fan AL, Myerowitz R et al (2008) Aptamer-based endocytosis of a lysosomal enzyme. Proc Natl Acad Sci U S A 105:15908–15913PubMedGoogle Scholar
  76. 76.
    Tong GJ, Hsiao SC, Carrico ZM, Francis MB (2009) Viral capsid DNA aptamer conjugates as multivalent cell-targeting vehicles. J Am Chem Soc 131:11174–11178PubMedGoogle Scholar
  77. 77.
    Huang YF, Chang HT, Tan W (2008) Cancer cell targeting using multiple aptamers conjugated on nanorods. Anal Chem 80:567–572PubMedGoogle Scholar
  78. 78.
    Wu Y, Phillips JA, Liu H, Yang R, Tan W (2008) Carbon nanotubes protect DNA strands during cellular delivery. ACS Nano 2:2023–2028PubMedGoogle Scholar
  79. 79.
    Kang H, O'Donoghue MB, Liu H, Tan W (2010) A liposome-based nanostructure for aptamer directed delivery. Chem Commun (Camb) 46:249–251Google Scholar
  80. 80.
    Cao Z, Tong R, Mishra A, Xu W, Wong GC, Cheng J, Lu Y (2009) Reversible cell-specific drug delivery with aptamer-functionalized liposomes. Angew Chem Int Ed Engl 48:6494–6498PubMedGoogle Scholar
  81. 81.
    Choi JH, Chen KH, Strano MS (2006) Aptamer-capped nanocrystal quantum dots: a new method for label-free protein detection. J Am Chem Soc 128:15584–15585PubMedGoogle Scholar
  82. 82.
    Park JU, Lee JH, Paik U, Lu Y, Rogers JA (2008) Nanoscale patterns of oligonucleotides formed by electrohydrodynamic jet printing with applications in biosensing and nanomaterials assembly. Nano Lett 8:4210–4216PubMedGoogle Scholar
  83. 83.
    Levy M, Cater SF, Ellington AD (2005) Quantum-dot aptamer beacons for the detection of proteins. Chem Biochem 6:2163–2166Google Scholar
  84. 84.
    Wernette DP, Liu J, Bohn PW, Lu Y (2008) Functional-DNA-based nanoscale materials and devices for sensing trace contaminants in water. MRS Bull 33:34–41Google Scholar
  85. 85.
    Li H, Wang C, Wu Z, Lu L, Qiu L, Zhou H, Shen G, Yu R (2013) An electronic channel switching-based aptasensor for ultrasensitive protein detection. Anal Chim Acta 758:130–137PubMedGoogle Scholar
  86. 86.
    Zhai L, Wang T, Kang K, Zhao Y, Shrotriya P, Nilsen-Hamilton M (2012) An RNA aptamer-based microcantilever sensor to detect the inflammatory marker, mouse lipocalin-2. Anal Chem 84:8763–8770PubMedGoogle Scholar
  87. 87.
    Swearingen CB, Wernette DP, Cropek DM, Lu Y, Sweedler JV, Bohn PW (2005) Immobilization of a catalytic DNA molecular beacon on Au for Pb(II) detection. Anal Chem 77:442–448PubMedGoogle Scholar
  88. 88.
    Du Y, Chen C, Zhou M, Dong S, Wang E (2011) Microfluidic electrochemical aptameric assay integrated on-chip: a potentially convenient sensing platform for the amplified and multiplex analysis of small molecules. Anal Chem 83:1523–1529PubMedGoogle Scholar
  89. 89.
    Mehan MR, Ostroff R, Wilcox SK, Steele F, Schneider D, Jarvis TC, Baird GS, Gold L, Janjic N (2013) Highly multiplexed proteomic platform for biomarker discovery, diagnostics, and therapeutics. Adv Exp Med Biol 734:283–300PubMedGoogle Scholar
  90. 90.
    Brody E, Gold L, Mehan M, Ostroff R, Rohloff J, Walker J, Zichi D (2012) Life's simple measures: unlocking the proteome. J Mol Biol 422:595–606PubMedGoogle Scholar
  91. 91.
    Liu J, Lee JH, Lu Y (2007) Quantum dot encoding of aptamer-linked nanostructures for one-pot simultaneous detection of multiple analytes. Anal Chem 79:4120–4125PubMedGoogle Scholar
  92. 92.
    Kuo TC, Cannon DM Jr, Chen Y, Tulock JJ, Shannon MA, Sweedler JV, Bohn PW (2003) Gateable nanofluidic interconnects for multilayered microfluidic separation systems. Anal Chem 75:1861–1867PubMedGoogle Scholar
  93. 93.
    Xu Y, Phillips JA, Yan J, Li Q, Fan ZH, Tan W (2009) Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells. Anal Chem 81:7436–7442PubMedGoogle Scholar
  94. 94.
    Stojanovic MN, Landry DW (2002) Aptamer-based colorimetric probe for cocaine. J Am Chem Soc 124:9678–9679PubMedGoogle Scholar
  95. 95.
    Wang Y, Li D, Ren W, Liu Z, Dong S, Wang E (2008) Ultrasensitive colorimetric detection of protein by aptamer-Au nanoparticles conjugates based on a dot-blot assay. Chem Commun (Camb) 44:2520–2522Google Scholar
  96. 96.
    Wang L, Liu X, Hu X, Song S, Fan C (2006) Unmodified gold nanoparticles as a colorimetric probe for potassium DNA aptamers. Chem Commun (Camb) 36:3780–3782Google Scholar
  97. 97.
    Wei H, Li B, Li J, Wang E, Dong S (2007) Simple and sensitive aptamer-based colorimetric sensing of protein using unmodified gold nanoparticle probes. Chem Commun (Camb) 36:3735–3737Google Scholar
  98. 98.
    Xue X, Wang F, Liu X (2008) One-step, room temperature, colorimetric detection of mercury (Hg2+) using DNA/nanoparticle conjugates. J Am Chem Soc 130:3244–3245PubMedGoogle Scholar
  99. 99.
    Tan YN, Su X, Zhu Y, Lee JY (2010) Sensing of transcription factor through controlled-assembly of metal nanoparticles modified with segmented DNA elements. ACS Nano 4:5101–5110PubMedGoogle Scholar
  100. 100.
    Jung Y, Kim T, Park H, Tom Soh H (2010) Specific colorimetric detection of proteins using bidentate aptamer-conjugated polydiacetylene (PDA) liposomes. Adv Funct Mater 20:3092–3097Google Scholar
  101. 101.
    Liu J, Mazumdar D, Lu Y (2006) A simple and sensitive “dipstick” test in serum based on lateral flow separation of aptamer-linked nanostructures. Angew Chem Int Ed Engl 45:7955–7959PubMedGoogle Scholar
  102. 102.
    Su S, Nutiu R, Filipe CD, Li Y, Pelton R (2007) Adsorption and covalent coupling of ATP-binding DNA aptamers onto cellulose. Langmuir 23:1300–1302PubMedGoogle Scholar
  103. 103.
    Patolsky F, Lichtenstein A, Willner I (2003) Highly sensitive amplified electronic detection of DNA by biocatalyzed precipitation of an insoluble product onto electrodes. Chemistry 9:1137–1145PubMedGoogle Scholar
  104. 104.
    Radi A (2011) Electrochemical aptamer-based biosensors: recent advances and perspectives. Int J Elect Article ID 863196Google Scholar
  105. 105.
    Min K, Song KM, Cho M, Chun YS, Shim YB, Ku JK, Ban C (2010) Simultaneous electrochemical detection of both PSMA (+) and PSMA (−) prostate cancer cells using an RNA/peptide dual-aptamer probe. Chem Commun (Camb) 46:5566–5568Google Scholar
  106. 106.
    Ilgu M, Wang T, Lamm M, Nilsen-Hamilton M (2013) Investigating the malleability of RNA aptamers. Methods. doi:10.1016/j.ymeth.2013.03.016 PubMedGoogle Scholar
  107. 107.
    Http://www.clinicaltrials.gov (2013). Accessed 5 June 13
  108. 108.
    Ni X, Castanares M, Mukherjee A, Lupold S (2011) Nucleic acid aptamers: clinical applications and promising new horizons. Curr Med Chem 18:4206–4214PubMedGoogle Scholar
  109. 109.
    Bae O-N (2012) Targeting von Willebrand factor as a novel anti-platelet therapy; application of ARC1779, an Anti-vWF aptamer, against thrombotic risk. Arch Pharm Res 35:1693–1699PubMedGoogle Scholar
  110. 110.
    Mayer G, Rohrbach F, Pötzsch B, Müller J (2011) Aptamer-based modulation of blood coagulation. Hamostaseologie 4:258–263Google Scholar
  111. 111.
    Cerchia L, Esposito C, Camorani S, Catuogno S, Franciscis V (2011) Coupling aptamers to short interfering RNAs as therapeutics. Pharmaceuticals 4:1434–1449Google Scholar
  112. 112.
    Zhou J, Bobbin M, Burnett J, Rossi J (2012) Current progress of RNA aptamer-based therapeutics. Front Genet 3:234PubMedGoogle Scholar
  113. 113.
    Esposito C, Catuogno S, Franciscis V, Cerchia L (2011) New insight into clinical development of nucleic acid aptamers. Discov Med 61:487–496Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Biology DepartmentIndian Institute of Science Education and Research (IISER)PuneIndia
  2. 2.Roy J Carver Department of Biochemistry, Biophysics and Molecular BiologyIowa State University and Ames LaboratoryAmesUSA

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