Abstract
Aptamers generated de novo by iterative process of in-vitro selection called Systemic Evolution of Ligand by EXponential enrichment (SELEX) which mimics Darwinian evolution process. SELEX is a powerful and yet simple technique that has been used to isolate DNA or RNA sequences with a function of interest (e.g. ligand-binding or catalysis) from a pool of random-sequence oligonucleotides based on their ability to bind to various types of different targets. Aptamers also known as chemicalbodies because of nature of selection and similarity in their action to antibodies. Aptamers have become attractive molecules in diagnostics and therapeutics rivaling and, in some cases, and extends many features of other molecular probes such as antibodies because of their nanomolar affinities and high specificities toward target molecule, amenable to various modifications, non-immunogenic nature and flexible structure properties. Recently, an increasing number of aptamers have been developed against various biomarkers expressed at the surface of mammalian cells or pathogenic microrganisms. This class of targets (mostly proteins) is associated with several pathologies including cancer, inflammation and infection diseases. Several of these aptamers were tested in-vivo as drugs or as targeting agents for site specific drug delivery, siRNA, microRNA or molecular imaging and may prove useful in the treatment of a wide variety of human maladies, including infectious diseases, cancer, and cardiovascular diseases. In this book chapter, we review the observations that expedited the development of this emerging class of therapeutics and speculate on the efficacy in the clinical studies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Akhtar S, Benter IF (2007) Nonviral delivery of synthetic siRNAs in vivo. J Clin Invest 117:3623–3632
Bagalkot V, Farokhzad OC, Langer R, Jon S (2006) An aptamer–doxorubicin physical conjugate as a novel targeted drug-delivery platform. Angew Chem 118:8329–8332
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 7:3065–3070
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 86:151–164
Berezhnoy A, Stewart CA, Mcnamara JO II, Thiel W, Giangrande P, Trinchieri G, Gilboa E (2012) Isolation and optimization of murine IL-10 receptor blocking oligonucleotide aptamers using high-throughput sequencing. Mol Ther 20:1242–1250
Boltz A, Piater B, Toleikis L, Guenther R, Kolmar H, Hock B (2011) Bi-specific aptamers mediating tumour cell lysis. J Biol Chem. M111. 238261
Borbas KE, Ferreira CS, Perkins A, Bruce JI, Missailidis S (2007) Design and synthesis of mono-and multimeric targeted radiopharmaceuticals based on novel cyclen ligands coupled to anti-MUC1 aptamers for the diagnostic imaging and targeted radiotherapy of cancer. Bioconjug Chem 18:1205–1212
Burmeister PE et al (2005) Direct in vitro selection of a 2′-O-methyl aptamer to VEGF. Chem Biol 12:25–33
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 48:6494–6498
Cerchia L, De Franciscis V (2010) Targeting cancer cells with nucleic acid aptamers. Trends Biotechnol 28:517–525
Charlton J, Sennello J, Smith D (1997) In vivo imaging of inflammation using an aptamer inhibitor of human neutrophil elastase. Chem Biol 4:809–816
Chen JJ, Lafrance ND, Allo MD, Cooper DS, Ladenson PW (1988) Single photon emission computed tomography of the thyroid. J Clin Endocrinol Metab 66:1240–1246
Chen HW et al (2008) Molecular recognition of small-cell lung cancer cells using aptamers. ChemMedChem 3:991–1001
Chen L, Li D, Zhong J, Wu X, Chen Q, Peng H, Liu S (2011) IL-17RA aptamer-mediated repression of IL-6 inhibits synovium inflammation in a murine model of osteoarthritis. Osteoarthr Cartil 19:711–718
Cibiel A, Pestourie C, Ducongé F (2012) In vivo uses of aptamers selected against cell surface biomarkers for therapy and molecular imaging. Biochimie 94:1595–1606
Da Pieve C, Perkins AC, Missailidis S (2009) Anti-MUC1 aptamers: radiolabelling with 99mTc and biodistribution in MCF-7 tumour-bearing mice. Nucl Med Biol 36:703–710
Da Rocha Gomes S et al (2012) 99mTc-MAG3-Aptamer for imaging human tumors associated with high level of matrix Metalloprotease-9. Bioconjug Chem 23:2192–2200
Dou X-Q et al (2018) Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity. Int J Nanomedicine 13:763
Dougherty CA, Cai W, Hong H (2015) Applications of aptamers in targeted imaging: state of the art. Curr Top Med Chem 15:1138–1152
Dua P, Kim S, Lee D-k (2011) Nucleic acid aptamers targeting cell-surface proteins. Methods 54:215–225
Dua P, Kang HS, Hong S-M, Tsao M-S, Kim S, Lee D-K (2013) Alkaline phosphatase ALPPL-2 is a novel pancreatic carcinoma-associated protein. Cancer Res 73(6):1934–1945
Erba PA, Israel O (2014) SPECT/CT in infection and inflammation. Clin Transl Imaging 2:519–535
Esposito CL et al (2011) A neutralizing RNA aptamer against EGFR causes selective apoptotic cell death. PLoS One 6:e24071
Famulok M, Hartig JS, Mayer G (2007) Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem Rev 107:3715–3743
Fan X, Sun L, Wu Y, Zhang L, Yang Z (2016) Bioactivity of 2′-deoxyinosine-incorporated aptamer AS1411. Sci Rep 6:25799
Fan X et al (2017) The bioactivity of d−/l-isonucleoside-and 2′-deoxyinosine-incorporated aptamer AS1411s including DNA replication/microrna expression. Mol Ther Nucleic Acids 9:218–229
Farokhzad OC, Jon S, Khademhosseini A, Tran T-NT, LaVan DA, Langer R (2004) Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer cells. Cancer Res 64:7668–7672
Ferrara N, Damico L, Shams N, Lowman H, Kim R (2006) Development of ranibizumab, an anti–vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 26:859–870
Ferreira CS, Cheung MC, Missailidis S, Bisland S, Gariepy J (2008) Phototoxic aptamers selectively enter and kill epithelial cancer cells. Nucleic Acids Res 37:866–876
Green LS et al (1995) Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor. Chem Biol 2:683–695
Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R (1994) Biodegradable long-circulating polymeric nanospheres. Science 263:1600–1603
Griffin LC, Tidmarsh GF, Bock LC, Toole JJ, Leung L (1993) In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits. Blood 81:3271–3276
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 117:727–735
Harding FA, Stickler MM, Razo J, DuBridge R (2010) The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs 3:256–265. Taylor & Francis
Hicke BJ, Stephens AW (2000) Escort aptamers: a delivery service for diagnosis and therapy. J Clin Invest 106:923–928
Hicke BJ et al (2006) Tumor targeting by an aptamer. J Nucl Med 47:668
Hong H, Goel S, Zhang Y, Cai W (2011) Molecular imaging with nucleic acid aptamers. Curr Med Chem 18:4195–4205
Hu P-P (2017) Recent advances in aptamers targeting immune system. Inflammation 40:295–302
Huang YF, Shangguan D, Liu H, Phillips JA, Zhang X, Chen Y, Tan W (2009) Molecular assembly of an aptamer–drug conjugate for targeted drug delivery to tumor cells. Chembiochem 10:862–868
Ireson CR, Kelland LR (2006) Discovery and development of anticancer aptamers. Mol Cancer Ther 5:2957–2962
Jacobson O et al (2015) PET imaging of tenascin-C with a radiolabeled single-stranded DNA aptamer. J Nucl Med 56:616
Jalalian SH, Ramezani M, Abnous K, Taghdisi SM (2018) Targeted co-delivery of epirubicin and NAS-24 aptamer to cancer cells using selenium nanoparticles for enhancing tumor response in vitro and in vivo. Cancer Lett 416:87–93
Javier DJ, Nitin N, Levy M, Ellington A, Richards-Kortum R (2008) Aptamer-targeted gold nanoparticles as molecular-specific contrast agents for reflectance imaging. Bioconjug Chem 19:1309–1312
Joshi R, Janagama H, Dwivedi HP, Kumar TS, Jaykus L-A, Schefers J, Sreevatsan S (2009) Selection, characterization, and application of DNA aptamers for the capture and detection of Salmonella enterica serovars. Mol Cell Probes 23:20–28
Kang D et al (2012) Selection of DNA aptamers against glioblastoma cells with high affinity and specificity. PLoS One 7:e42731
Keefe AD, Pai S, Ellington A (2010) Aptamers as therapeutics. Nat Rev Drug Discov 9:537
Keidar Z, Israel O, Krausz Y (2003) SPECT/CT in tumor imaging: technical aspects and clinical applications. Semin Nucl Med 3:205–218. Elsevier
Kim D, Jeong YY, Jon S (2010) A drug-loaded aptamer− gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano 4:3689–3696
Kim JK, Choi K-J, Lee M, Jo M-h, Kim S (2012) Molecular imaging of a cancer-targeting theragnostics probe using a nucleolin aptamer-and microRNA-221 molecular beacon-conjugated nanoparticle. Biomaterials 33:207–217
Ko HY, Lee JH, Kang H, Ryu SH, Song IC, Lee DS, Kim S (2010) A nucleolin-targeted multimodal nanoparticle imaging probe for tracking cancer cells using an aptamer. J Nucl Med 51:98–105
Koo V, Hamilton P, Williamson K (2006) Non-invasive in vivo imaging in small animal research. Anal Cell Pathol 28:127–139
Koutsioumpa M, Papadimitriou E (2014) Cell surface nucleolin as a target for anti-cancer therapies. Recent Pat Anticancer Drug Discov 9:137–152
Kryza D et al (2016) Ex vivo and in vivo imaging and biodistribution of aptamers targeting the human matrix metalloprotease-9 in melanomas. PLoS One 11:e0149387
Kumar P, Lambadi PR, Navani NK (2015) Non-enzymatic detection of urea using unmodified gold nanoparticles based aptasensor. Biosens Bioelectron 72:340–347
Lange CW, VanBrocklin HF, Taylor SE (2002) Photoconjugation of 3-azido-5-nitrobenzyl-[18F] fluoride to an oligonucleotide aptamer. J Label Compd Radiopharm 45:257–268
Lao Y-H, Phua KK, Leong KW (2015) Aptamer nanomedicine for cancer therapeutics: barriers and potential for translation. ACS Nano 9:2235–2254
Lee JW, Kim HJ, Heo K (2015) Therapeutic aptamers: developmental potential as anticancer drugs. BMB Rep 48:234
Li L et al (2010) Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia. J Control Release 143:274–279
Li N, Nguyen HH, Byrom M, Ellington AD (2011) Inhibition of cell proliferation by an anti-EGFR aptamer. PLoS One 6:e20299
Li X, Zhang X-N, Li X-D, Chang J (2016) Multimodality imaging in nanomedicine and nanotheranostics. Cancer Biol Med 13:339
Liu Z, Duan J-H, Song Y-M, Ma J, Wang F-D, Lu X, Yang X-D (2012) Novel HER2 aptamer selectively delivers cytotoxic drug to HER2-positive breast cancer cells in vitro. J Transl Med 10:148
Maisonpierre PC et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60
Mann AP et al (2010) Identification of thioaptamer ligand against E-selectin: potential application for inflamed vasculature targeting. PLoS One 5:e13050
McNamara JO et al (2008) Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J Clin Invest 118:376–386
Mongelard F, Bouvet P (2010) AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia. Curr Opin Mol Ther 12:107–114
Morita Y, Leslie M, Kameyama H, Volk DE, Tanaka T (2018) Aptamer therapeutics in Cancer: current and future. Cancers 10:80
Mor-Vaknin N et al (2017) DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis. Nat Commun 8:14252
Navani NK, Li Y (2006) Nucleic acid aptamers and enzymes as sensors. Curr Opin Chem Biol 10:272–281
Nimjee SM, White RR, Becker RC, Sullenger BA (2017) Aptamers as therapeutics. Annu Rev Pharmacol Toxicol 57:61–79
Orava EW, Cicmil N, Gariépy J (2010) Delivering cargoes into cancer cells using DNA aptamers targeting internalized surface portals. Biochim Biophys Acta Biomembr 1798:2190–2200
Osborne SE, Matsumura I, Ellington AD (1997) Aptamers as therapeutic and diagnostic reagents: problems and prospects. Curr Opin Chem Biol 1:5–9
Parekh P, Kamble S, Zhao N, Zeng Z, Portier BP, Zu Y (2013) Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer. Biomaterials 34:8909–8917
Pastor F et al. (2013) CD28 aptamers as powerful immune response modulators. Mol Ther Nucleic Acids 2
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751
Poolsup S, Kim C-Y (2017) Therapeutic applications of synthetic nucleic acid aptamers. Curr Opin Biotechnol 48:180–186
Porciani D, Tedeschi L, Marchetti L, Citti L, Piazza V, Beltram F, Signore G (2015) Aptamer-mediated codelivery of doxorubicin and NF-κB decoy enhances chemosensitivity of pancreatic tumor cells. Mol Ther Nucleic Acids:4
Prusty DK, Adam V, Zadegan RM, Irsen S, Famulok M (2018) Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells. Nat Commun 9:535
Queirós RB, de-Los-Santos-Álvarez N, Noronha J, MGF S (2013) A label-free DNA aptamer-based impedance biosensor for the detection of E coli outer membrane proteins. Sensors Actuators B Chem 181:766–772
Rahmim A, Zaidi H (2008) PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun 29:193–207
Reyes-Reyes E, Šalipur FR, Shams M, Forsthoefel MK, Bates PJ (2015) Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation. Mol Oncol 9:1392–1405
Rollo F (2003) Molecular imaging: an overview and clinical applications. Radiol Manage 25:28–32. quiz 33-25
Röthlisberger P, Gasse C, Hollenstein M (2017) Nucleic acid aptamers: emerging applications in medical imaging, nanotechnology, neurosciences, and drug delivery. Int J Mol Sci 18:2430
Ruckman 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 273:20556–20567
Savla R, Taratula O, Garbuzenko O, Minko T (2011) Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer. J Control Release 153:16–22. https://doi.org/10.1016/j.jconrel.2011.02.015
Sayyed S et al (2009) Podocytes produce homeostatic chemokine stromal cell-derived factor-1/CXCL12, which contributes to glomerulosclerosis, podocyte loss and albuminuria in a mouse model of type 2 diabetes. Diabetologia 52:2445–2454
Sefah K, Shangguan D, Xiong X, O’donoghue MB, Tan W (2010) Development of DNA aptamers using Cell-SELEX. Nat Protoc 5:1169
Shangguan D et al (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci 103:11838–11843
Shi H et al (2010) In vivo fluorescence imaging of tumors using molecular aptamers generated by cell-SELEX. Chem Asian J 5:2209–2213
Shi H et al (2011) Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration. Proc Natl Acad Sci 108:3900–3905
Shigdar S et al (2013) RNA aptamers targeting cancer stem cell marker CD133. Cancer Lett 330:84–95
Singh SK, Singh S, Lillard JW Jr, Singh R (2017) Drug delivery approaches for breast cancer. Int J Nanomedicine 12:6205
Song Y et al (2013) Selection of DNA aptamers against epithelial cell adhesion molecule for cancer cell imaging and circulating tumor cell capture. Anal Chem 85:4141–4149
Swierczewska M, Lee S, Chen X (2011) Inorganic nanoparticles for multimodal molecular imaging. Mol Imaging 10:7290.2011. 00001
Thiel KW et al (2012) Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers. Nucleic Acids Res 40:6319–6337
Wang AZ, Farokhzad OC (2014) Current progress of aptamer-based molecular imaging. J Nucl Med 55:353
Wang Y, Li Z, Hu D, Lin C-T, Li J, Lin Y (2010) Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. J Am Chem Soc 132:9274–9276
Wang B et al (2016) Aptamer induced assembly of fluorescent nitrogen-doped carbon dots on gold nanoparticles for sensitive detection of AFB1. Biosens Bioelectron 78:23–30
Watson SR, Chang Y-F, O’connell D, Weigand L, Ringquist S, Parma D (2000) Anti-L-selectin aptamers: binding characteristics, pharmacokinetic parameters, and activity against an intravascular target in vivo. Antisense Nucleic Acid Drug Dev 10:63–75
Willis MC et al (1998) Liposome-anchored vascular endothelial growth factor aptamers. Bioconjug Chem 9:573–582
Wilner SE et al (2012) An RNA alternative to human transferrin: a new tool for targeting human cells. Mol Ther Nucleic Acids:1
Wu Y, Sefah K, Liu H, Wang R, Tan W (2010) DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells. Proc Natl Acad Sci 107:5–10
Yu MK, Kim D, Lee IH, So JS, Jeong YY, Jon S (2011) Image-guided prostate cancer therapy using aptamer-functionalized thermally cross-linked superparamagnetic iron oxide nanoparticles. Small 7:2241–2249
Zamay TN et al (2014) DNA-aptamer targeting vimentin for tumor therapy in vivo. Nucleic Acid Ther 24:160–170
Zhou J, Rossi J (2017) Aptamers as targeted therapeutics: current potential and challenges. Nat Rev Drug Discov 16:181
Zhou J, Bobbin M, Burnett JC, Rossi JJ (2012) Current progress of RNA aptamer-based therapeutics. Front Genet 3:234
Zhou J et al (2013) Dual functional BAFF receptor aptamers inhibit ligand-induced proliferation and deliver siRNAs to NHL cells. Nucleic Acids Res 41:4266–4283
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Baba, S.A. et al. (2019). Nucleic Acid Guided Molecular Tool for In-Vivo Theranostic Applications. In: Yadav, G., Kumar, V., Aggarwal, N. (eds) Aptamers. Springer, Singapore. https://doi.org/10.1007/978-981-13-8836-1_7
Download citation
DOI: https://doi.org/10.1007/978-981-13-8836-1_7
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-8835-4
Online ISBN: 978-981-13-8836-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)