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RNA Aptamers: A Review of Recent Trends and Applications

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Future Trends in Biotechnology

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 131))

Abstract

RNA aptamers, small oligonucleotides derived by an in-vitro selection process called SELEX (Systematic Evolution of Ligands by EXperimental enrichment), are important candidates for therapeutic and diagnostic applications. RNA aptamers have high affinity and specificity for their target molecules. In this review, we describe methods for generating RNA aptamers (the SELEX technique and modified SELEX processes) and therapeutic applications for diseases such as neovascular age-related macular degeneration (AMD), inflammatory diseases, and obesity. We also analyze the social networks among researchers and organizations (universities, research institutes, firms, etc.) that are active in the pursuit of aptamer-based therapeutic approaches. This study provides relevant information on recent research trends in RNA aptamers.

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Abbreviations

CAD:

Coronary artery disease

CNV:

Choroidal neovascularization

MCP-1:

Monocyte chemoattractant Protein 1

NIH:

National Institutes of Health

OECD:

Organization for Economic Cooperation and Development

PCI:

Percutaneous coronary intervention

PEG:

Polyethylene glycol

RADAR:

A Randomized, partially-blinded, multi-center, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system compared to unfractionated heparin or low molecular heparin in subjects with acute coronary syndromes

SDF-1:

Stromal cell-derived factor-1

SELEX:

Systematic evolution of ligands by exponential enrichment

SMEs:

Small- and medium-sized enterprises

VEGF:

Vascular endothelial growth factor

References

  1. Bunka DHJ, Stockley PG (2006) Aptamers come of age––at last. Nat Rev Microbiol 4:588–596

    Article  CAS  Google Scholar 

  2. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822

    Article  CAS  Google Scholar 

  3. Robertson DL, Joyce GF (1990) Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344:467–468

    Article  CAS  Google Scholar 

  4. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA-polymerase. Science 249:505–510

    Article  CAS  Google Scholar 

  5. Vater A, Klussman S (2003) Toward third-generation aptamers: Spiegelmers and their therapeutic prospects. Curr Opin Drug Discov Devel 6:253–261

    CAS  Google Scholar 

  6. Ulrich H (2006) RNA aptamers: from basic science towards therapy. Handb Exp Pharmacol 173:305–326

    Article  CAS  Google Scholar 

  7. Bunka DHJ, Platonova O, Stockley PG (2010) Development of aptamer therapeutics. Curr Opin Pharmacol 10:557–562

    Article  CAS  Google Scholar 

  8. Cox JC, Hayhurst A, Hesselberth J et al (2002) Automated selection of aptamers against protein targets translated in vitro: from gene to aptamer. Nucleic Acids Res 30:e108

    Article  Google Scholar 

  9. Yang Y, Yang D, Schluesener HJ et al (2007) Advances in SELEX and application of aptamers in the central nervous system. Biomol Eng 24(6):583–592

    Article  CAS  Google Scholar 

  10. White R, Rusconi C, Scardino E et al (2001) Generation of species cross-reactive aptamers using “Toggle” SELEX. Mol Ther 4:567–573

    Article  CAS  Google Scholar 

  11. Vater A, Jarosch F, Buchner K et al (2003) Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: tailored-SELEX. Nucleic Acids Res 31:e130

    Article  Google Scholar 

  12. Fruste JP, Bald R, Erdmann VA (2002) Mirror-symmetrical selection and evolution of nucleic acids. EP-00934331

    Google Scholar 

  13. Ng EWM, Shima DT, Calias P et al (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 5(2):123–132

    Article  CAS  Google Scholar 

  14. Lee JF, Stovall GM, Ellington AD (2006) Aptamer therapeutics advance. Curr Opin Chem Biol 10(3):282–289

    Article  CAS  Google Scholar 

  15. Bless NM, Smith D, Charlton J et al (1997) Protective effects of an aptamer inhibitor of neutrophil elastase in lung inflammatory injury. Curr Biol 7:877–880

    Article  CAS  Google Scholar 

  16. Kourlas H, Schiller DS (2006) Pegaptanib sodium for the treatment of neovascular age-related macular degeneration: a review. Clin Ther 28(1):36–44

    Article  CAS  Google Scholar 

  17. Gragoudas ES, Adamis AP, Cunningham ET Jr et al (2004) Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 351:2805–2816

    Article  CAS  Google Scholar 

  18. Tucker CE, Chen L-S, Judkins MB et al (1999) Detection and plasma pharmacokinetics of an anti-vascular endothelial growth factor oligonucleotide-aptamer (NX1838) in rhesus monkeys. J Chromatogr B Biomed Sci Appl 732:203–212

    Article  CAS  Google Scholar 

  19. Ruckman J, Green LS, Beeson J et al (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

    Article  CAS  Google Scholar 

  20. Drolet DW, Nelson J, Tucker CE et al (2000) Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys. Pharm Res 17(12):1503–1510

    Article  CAS  Google Scholar 

  21. Vinores SA (2003) Technology evaluation: pegaptanib Eyetech/Pfizer. Curr Opin Mol Ther 5(6):673–679

    CAS  Google Scholar 

  22. Eyetech Study Group (2002) Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina 22:143–152

    Article  Google Scholar 

  23. 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

    Article  Google Scholar 

  24. Rusconi CP, Roberts JD, Pitoc GA et al (2004) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnol 22:1423–1428

    Article  CAS  Google Scholar 

  25. Rusconi CP, Scardino E, Layzer J et al (2002) RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 419:90–94

    Article  CAS  Google Scholar 

  26. Dyke CK, Steinhubl SR, Kleiman NS et al (2006) 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 114(23):2490–2497

    Article  CAS  Google Scholar 

  27. Chan MY, Rusconi CP, Alexander JH et al (2008) A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor. J Thromb Haemost 6:789–796

    Article  CAS  Google Scholar 

  28. Chan MY, Cohen MG, Dyke CK et al (2008) Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. Circulation 117(22):2865–2874

    Article  CAS  Google Scholar 

  29. Povsic TJ, Cohen MG, Chan MY et al (2011) Dose selection for a direct and selective factor IXa inhibitor and its complementary reversal agent: translating pharmacokinetic and pharmacodynamic properties of the REG1system to clinical trial design. J Thromb Thrombolysis 32:21–31

    Article  CAS  Google Scholar 

  30. Cohen MG, Purdy DA, Rossi JS et al (2010) First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention. Circulation 122(6):614–622

    Article  CAS  Google Scholar 

  31. Povsic TJ, Wargin WA, Alexander JH et al (2011) Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy. Eur Heart J 32(19):2412–2419

    Article  CAS  Google Scholar 

  32. Kulkarni O, Pawar RD, Purschke W et al (2007) Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice. J Am Soc Nephrol 18:2350–2358

    Article  CAS  Google Scholar 

  33. Ninichuk V, Clauss S, Kulkarni O et al (2008) Late onset of Ccl2 blockade with the spiegelmer mNOX-E36–3′PEG prevents glomerulosclerosis and improves glomerular filtration rate in db/db mice. Am J Pathol 172(3):628–637

    Article  CAS  Google Scholar 

  34. NOXXON homepage http://145.253.103.53/noxxon16/downloads/FactSheet.pdf

  35. Ophthotech homepage http://www.ophthotech.com/products/arc1905/

  36. Drolet DW, Moon-McDermott L, Romig TS (1996) An enzyme-linked oligonucleotide assay. Nat Biotechnol 14:1021–1025

    Article  CAS  Google Scholar 

  37. McCauley TG, Hamaguchi N, Stanton M (2003) Aptamer-based biosensor arrays for detection and quantification of biological macromolecules. Anal Biochem 319:244–250

    Article  CAS  Google Scholar 

  38. Ulrich H, Martins AH, Pesquero JB (2004) RNA and DNA aptamers in cytomics analysis. Cytometry A 59:220–231

    Article  Google Scholar 

  39. Davis KA, Lin Y, Abrams B et al (1998) Staining of cell surface human CD4 with 2′-F-pyrimidine-containing RNA aptamers for flow cytometry. Nucleic Acids Res 26(17):3915–3924

    Article  CAS  Google Scholar 

  40. Bagalkot V, Zhang L, Levy-Nissenbaum E et al (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(10):3065–3070

    Article  CAS  Google Scholar 

  41. Gold L, Ayers D, Bertino J et al (2010) Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS ONE 5(12):e15004. doi:10.1371/journal.pone.0015004

    Article  CAS  Google Scholar 

  42. NIH homepage www.nih.gov/news/researchtools/

  43. OECD homepage www.oecd.org/dataoecd/39/38/36198812.pdf

  44. Kang KN, Ryu TK, Lee YS (2009) Effects of research tool patents on biotechnology innovation in a developing country: a case study of South Korea. BMC Biotechnol 9:25

    Article  Google Scholar 

  45. Nimjee 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 14(3):408–415

    Article  CAS  Google Scholar 

  46. Kulkarni O, Eulberg D, Selve N et al (2009) Anti-Ccl2 Spiegelmer permits 75% dose reduction of cyclophosphamide to control diffuse proliferative lupus nephritis and pneumonitis in MRL-Fas(lpr) mice. J Pharmacol Exp Ther 28(2):371–377

    Article  Google Scholar 

  47. Clauss S, Gross O, Kulkarni O et al (2009) Ccl2/Mcp-1 blockade reduces glomerular and interstitial macrophages but does not ameliorate renal pathology in collagen4A3-deficient mice with autosomal recessive Alport nephropathy. J Pathol 218(1):40–47

    Article  CAS  Google Scholar 

  48. Baum JAC, Calabrese T, Silverman BS (2000) Don’t go it alone: alliance network composition and startup’s performance in Canadian biotechnology. Strateg Manag J 21:267–294

    Article  Google Scholar 

  49. George G, Zahra SA, Wood DR (2002) The effects of business–university alliances on innovative output and financial performance: a study of publicly traded biotechnology companies. J Bus Ventur 17:577–609

    Article  Google Scholar 

  50. Hagedoorn J (1993) Understanding the rationale of strategic technology partnering: interorganizational modes of cooperation and sectoral differences. Strateg Manag J 14:371–385

    Article  Google Scholar 

  51. Romijn H, Albaladejo M (2002) Determinants of innovation capability in small electronics and software firms in Southeast England. Res Policy 31:1053–1067

    Article  Google Scholar 

  52. Rothaermel FT, Deeds DL (2006) Alliance type, alliance experience and alliance management capability in high-technology ventures. J Bus Ventur 21:429–460

    Article  Google Scholar 

  53. Shan W, Walker G, Kogut B (1994) Interfirm cooperation and startup innovation in the biotechnology industry. Strateg Manag J 15:387–394

    Article  Google Scholar 

  54. Becheikh N, Landry R, Amara N (2006) Lessons from innovation empirical studies in the manufacturing sector: a systematic review of the literature from 1993–2003. Technovation 26:644–664

    Article  Google Scholar 

  55. Kang KN, Lee YS (2008) What affects the innovation performance of small and medium-sized enterprises (SMEs) in the biotechnology industry? An empirical study on Korean biotech SMEs. Biotechnol Lett 30:1699–1704

    Article  CAS  Google Scholar 

  56. Azoulay P, Ding W, Stuart T (2007) The determinants of faculty patenting behavior: demographics or opportunities? J Econ Behav Organ 63:599–623

    Article  Google Scholar 

  57. Zucker LG, Darby MR (2001) Capturing technological opportunity via Japan’s star scientists: evidence from Japanese firms’ biotech patents and products. J Technol Transf 26(1–2):37–58

    Article  Google Scholar 

  58. Zucker LG, Darby MR, Brewer MB (1998) Intellectual human capital and the birth of U.S. biotechnology enterprises. Am Econ Rev 88(1):290–306

    Google Scholar 

  59. Zucker LG, Darby MR, Armstrong JS (2002) Commercializing knowledge: university science, knowledge capture, and firm performance in biotechnology. Manag Sci 48(1):138–153

    Article  Google Scholar 

  60. BCC Research (2010) Nucleic acid aptamers for diagnostics and therapeutics: global markets. (Report BIO071A)

    Google Scholar 

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Authors and Affiliations

  1. Korea Institute of Intellectual Property, KIPS Center, 9th FL. 647-9, Yeoksam-dong, Gangnam-gu, Seoul, 135-980, Korea

    Kyung-Nam Kang

  2. School of Chemical and Biological Engineering, Seoul National University, Seoul, 151-747, Korea

    Yoon-Sik Lee

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  1. Kyung-Nam Kang
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Correspondence to Yoon-Sik Lee .

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Editors and Affiliations

  1. School of Life Sciences & Biotechnology, Bio-Building #3-311, Shanghai Jiao Tong University, Dong-Chuan Road 800, Shanghai, 200240, China, People's Republic

    Jian-Jiang Zhong

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Kang, KN., Lee, YS. (2012). RNA Aptamers: A Review of Recent Trends and Applications. In: Zhong, JJ. (eds) Future Trends in Biotechnology. Advances in Biochemical Engineering/Biotechnology, vol 131. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2012_136

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