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
Bunka DHJ, Stockley PG (2006) Aptamers come of age––at last. Nat Rev Microbiol 4:588–596
Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822
Robertson DL, Joyce GF (1990) Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344:467–468
Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA-polymerase. Science 249:505–510
Vater A, Klussman S (2003) Toward third-generation aptamers: Spiegelmers and their therapeutic prospects. Curr Opin Drug Discov Devel 6:253–261
Ulrich H (2006) RNA aptamers: from basic science towards therapy. Handb Exp Pharmacol 173:305–326
Bunka DHJ, Platonova O, Stockley PG (2010) Development of aptamer therapeutics. Curr Opin Pharmacol 10:557–562
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
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
White R, Rusconi C, Scardino E et al (2001) Generation of species cross-reactive aptamers using “Toggle” SELEX. Mol Ther 4:567–573
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
Fruste JP, Bald R, Erdmann VA (2002) Mirror-symmetrical selection and evolution of nucleic acids. EP-00934331
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
Lee JF, Stovall GM, Ellington AD (2006) Aptamer therapeutics advance. Curr Opin Chem Biol 10(3):282–289
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
Kourlas H, Schiller DS (2006) Pegaptanib sodium for the treatment of neovascular age-related macular degeneration: a review. Clin Ther 28(1):36–44
Gragoudas ES, Adamis AP, Cunningham ET Jr et al (2004) Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 351:2805–2816
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
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
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
Vinores SA (2003) Technology evaluation: pegaptanib Eyetech/Pfizer. Curr Opin Mol Ther 5(6):673–679
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
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
Rusconi CP, Roberts JD, Pitoc GA et al (2004) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnol 22:1423–1428
Rusconi CP, Scardino E, Layzer J et al (2002) RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 419:90–94
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
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
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
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
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
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
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
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
NOXXON homepage http://145.253.103.53/noxxon16/downloads/FactSheet.pdf
Ophthotech homepage http://www.ophthotech.com/products/arc1905/
Drolet DW, Moon-McDermott L, Romig TS (1996) An enzyme-linked oligonucleotide assay. Nat Biotechnol 14:1021–1025
McCauley TG, Hamaguchi N, Stanton M (2003) Aptamer-based biosensor arrays for detection and quantification of biological macromolecules. Anal Biochem 319:244–250
Ulrich H, Martins AH, Pesquero JB (2004) RNA and DNA aptamers in cytomics analysis. Cytometry A 59:220–231
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
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
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
NIH homepage www.nih.gov/news/researchtools/
OECD homepage www.oecd.org/dataoecd/39/38/36198812.pdf
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
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
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
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
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
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
Hagedoorn J (1993) Understanding the rationale of strategic technology partnering: interorganizational modes of cooperation and sectoral differences. Strateg Manag J 14:371–385
Romijn H, Albaladejo M (2002) Determinants of innovation capability in small electronics and software firms in Southeast England. Res Policy 31:1053–1067
Rothaermel FT, Deeds DL (2006) Alliance type, alliance experience and alliance management capability in high-technology ventures. J Bus Ventur 21:429–460
Shan W, Walker G, Kogut B (1994) Interfirm cooperation and startup innovation in the biotechnology industry. Strateg Manag J 15:387–394
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
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
Azoulay P, Ding W, Stuart T (2007) The determinants of faculty patenting behavior: demographics or opportunities? J Econ Behav Organ 63:599–623
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
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
Zucker LG, Darby MR, Armstrong JS (2002) Commercializing knowledge: university science, knowledge capture, and firm performance in biotechnology. Manag Sci 48(1):138–153
BCC Research (2010) Nucleic acid aptamers for diagnostics and therapeutics: global markets. (Report BIO071A)
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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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DOI: https://doi.org/10.1007/10_2012_136
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