[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.4062/biomolther.2013.085

Nucleic Acid Aptamers: New Methods for Selection, Stabilization, and Application in Biomedical Science

Kong, Hoon Young (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University)
Byun, Jonghoe (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University)

Publication Information

Biomolecules & Therapeutics / v.21, no.6, 2013 , pp. 423-434 More about this Journal

Abstract

The adoption of oligonucleotide aptamer is well on the rise, serving an ever increasing demand for versatility in biomedical field. Through the SELEX (Systematic Evolution of Ligands by EXponential enrichment), aptamer that can bind to specific target with high affinity and specificity can be obtained. Aptamers are single-stranded nucleic acid molecules that can fold into complex three-dimensional structures, forming binding pockets and clefts for the specific recognition and tight binding of any given molecular target. Recently, aptamers have attracted much attention because they not only have all of the advantages of antibodies, but also have unique merits such as thermal stability, ease of synthesis, reversibility, and little immunogenicity. The advent of novel technologies is revolutionizing aptamer applications. Aptamers can be easily modified by various chemical reactions to introduce functional groups and/or nucleotide extensions. They can also be conjugated to therapeutic molecules such as drugs, drug containing carriers, toxins, or photosensitizers. Here, we discuss new SELEX strategies and stabilization methods as well as applications in drug delivery and molecular imaging.

Keywords

Aptamer; Stabilization; Modification; SELEX; Imaging; Drug delivery system;

Citations & Related Records

Reference

1	Nolte, A., Klussmann, S., Bald, R., Erdmann, V. A. and Furste, J. P. (1996) Mirror-design of L-oligonucleotide ligands binding to L-arginine. Nat. Biotechnol. 14, 1116-1119. DOI ScienceOn
2	Pageau, S. C. (2009) Denosumab. MAbs 1, 210-5. DOI
3	Park, S. M., Ahn, J. Y., Jo, M., Lee, D. K., Lis, J. T., Craighead, H. G. and Kim, S. (2009) Selection and elution of aptamers using nanoporous sol-gel arrays with integrated microheaters. Lab Chip 9, 1206-1212. DOI ScienceOn
4	Pastor, F., Soldevilla, M. M., Villanueva, H., Kolonias, D., Inoges, S., de Cerio, A. L., Kandzia, R., Klimyuk, V., Gleba, Y., Gilboa, E. and Bendandi, M. (2013) CD28 aptamers as powerful immune response modulators. Mol. Ther. Nucleic Acids 2, e98. DOI ScienceOn
5	Rockey, W. M., Huang, L., Kloepping, K. C., Baumhover, N. J., Giangrande, P. H. and Schultz, M. K. (2011) Synthesis and radiolabeling of chelator-RNA aptamer bioconjugates with copper-64 for targeted molecular imaging. Bioorg. Med. Chem. 19, 4080-4090. DOI ScienceOn
6	Romer, P. S., Berr, S., Avota, E., Na, S. Y., Battaglia, M., ten Berge, I., Einsele, H. and Hunig, T. (2011) Preculture of PBMCs at high cell density increases sensitivity of T-cell responses, revealing cytokine release by CD28 superagonist TGN1412. Blood 118, 6772-6782. DOI
7	Ruckman, J., Green, L. S., Beeson, J., Waugh, S., Gillette, W. L., Henninger, D. D., Claesson-Welsh, L. and 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, 20556-20567. DOI ScienceOn
8	Savla, R., Taratula, O., Garbuzenko, O. and Minko, T. (2011) Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer. J. Control. Release 153, 16-22. DOI ScienceOn
9	Schmidt, K. S., Borkowski, S., Kurreck, J., Stephens, A. W., Bald, R., Hecht, M., Friebe, M., Dinkelborg, L. and Erdmann, V. A. (2004) Application of locked nucleic acids to improve aptamer in vivo stability and targeting function. Nucleic Acids Res. 32, 5757-5765. DOI ScienceOn
10	Schneider, D. J., Feigon, J., Hostomsky, Z. and Gold, L. (1995) Highaffi nity ssDNA inhibitors of the reverse transcriptase of type 1 human immunodefi ciency virus. Biochemistry 34, 9599-9610. DOI ScienceOn
11	Shi, H., Tang, Z., Kim, Y., Nie, H., Huang, Y. F., He, X., Deng, K., Wang, K. and Tan, W. (2010) in vivo fl uorescence imaging of tumors using molecular aptamers generated by cell-SELEX. Chem. Asian J. 5, 2209-2213. DOI ScienceOn
12	Shoji, A., Kuwahara, M., Ozaki, H. and Sawai, H. (2007) Modified DNA aptamer that binds the (R)-isomer of a thalidomide derivative with high enantioselectivity. J. Am. Chem. Soc. 129, 1456-1464. DOI ScienceOn
13	Siller-Matula, J. M., Merhi, Y., Tanguay, J. F., Duerschmied, D., Wagner, D. D., McGinness, K. E., Pendergrast, P. S., Chung, J. K., Tian, X., Schaub, R. G. and Jilma, B. (2012) ARC15105 is a potent antagonist of von Willebrand factor mediated platelet activation and adhesion. Arterioscler. Thromb. Vasc. Biol. 32, 902-909. DOI
14	Song, Y., Zhu, Z., An, Y., Zhang, W., Zhang, H., Liu, D., Yu, C., Duan, W. and Yang, C. J. (2013) Selection of DNA aptamers against epithelial cell adhesion molecule for cancer cell imaging and circulating tumor cell capture. Anal. Chem. 85, 4141-4149. DOI ScienceOn
15	Subramanian, N., Raghunathan, V., Kanwar, J. R., Kanwar, R. K., Elchuri, S. V., Khetan, V. and Krishnakumar, S. (2012) Target-specific delivery of doxorubicin to retinoblastoma using epithelial cell adhesion molecule aptamer. Mol. Vis. 18, 2783-2795.
16	Suntharalingam, G., Perry, M. R., Ward, S., Brett, S. J., Castello-Cortes, A., Brunner, M. D. and Panoskaltsis, N. (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med. 355, 1018-1028. DOI ScienceOn
17	Bagalkot, V., Farokhzad, O. C., Langer, R. and Jon, S. (2006) An aptamer-doxorubicin physical conjugate as a novel targeted drugdelivery platform. Angew. Chem. Int. Ed. Engl. 45, 8149-8152. DOI ScienceOn
18	Berezovski, M., Musheev, M., Drabovich, A. and Krylov, S. N. (2006) Non-SELEX selection of aptamers. J. Am. Chem. Soc. 128, 1410-1411. DOI ScienceOn
19	Andreola, M. L., Calmels, C., Michel, J., Toulme, J. J. and Litvak, S. (2000) Towards the selection of phosphorothioate aptamers:optimizing in vitro selection steps with phosphorothioate nucleotides. Eur. J. Biochem. 267, 5032-5040. DOI ScienceOn
20	Aravind, A., Jeyamohan, P., Nair, R., Veeranarayanan, S., Nagaoka, Y., Yoshida, Y., Maekawa, T. and Kumar, D. S. (2012) AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery. Biotechnol. Bioeng. 109, 2920-2931. DOI ScienceOn
21	Banaszynski, M. and Kolesar, J. M. (2013) Vemurafenib and ipilimumab: New agents for metastatic melanoma. Am. J. Health Syst. Pharm. 70, 1205-1210. DOI ScienceOn
22	Barciszewski, J., Medgaard, M., Koch, T., Kurreck, J. and Ermann, V. A. (2009) Locked nucleic acid aptamers. Methods Mol. Biol. 535, 165-186. DOI ScienceOn
23	Tsien, R. Y. (2005) Building and breeding molecules to spy on cells and tumors. FEBS Lett. 579, 927-932. DOI ScienceOn
24	Talbot, L. J., Mi, Z., Bhattacharya, S. D., Kim, V., Guo, H. and Kuo, P. C. (2011) Pharmacokinetic characterization of an RNA aptamer against osteopontin and demonstration of in vivo effi cacy in reversing growth of human breast cancer cells. Surgery 150, 224-230. DOI ScienceOn
25	Tang, Z., Parekh, P., Turner, P., Moyer, R. W. and Tan, W. (2009) Generating aptamers for recognition of virus-infected cells. Clin. Chem. 55, 813-822. DOI ScienceOn
26	Tsai, C. H., Chen, J. and Szostak, J. W. (2007) Enzymatic synthesis of DNA on glycerol nucleic acid templates without stable duplex formation between product and template. Proc. Natl. Acad. Sci. USA 104, 14598-14603. DOI ScienceOn
27	Tuerk, C. and Gold, L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505-510. DOI
28	Vater, A., Sell, S., Kaczmarek, P., Maasch, C., Buchner, K., Pruszynska-Oszmalek, E., Kolodziejski, P., Purschke, W. G., Nowak, K. W., Strowski, M. Z. and Klussmann, S. (2013) A mixed mirror-image DNA/RNA aptamer inhibits glucagon and acutely improves glucose tolerance in models of type 1 and type 2 diabetes. J. Biol. Chem. 288, 21136-21147. DOI ScienceOn
29	Vaught, J. D., Bock, C., Carter, J., Fitzwater, T., Otis, M., Schneider, D., Rolando, J., Waugh, S., Wilcox, S. K. and Eaton, B. E. (2010) Expanding the chemistry of DNA for in vitro selection. J. Am. Chem. Soc. 132, 4141-4151. DOI ScienceOn
30	Veedu, R. N., Vester, B. and Wengel, J. (2009) Effi cient enzymatic synthesis of LNA-modified DNA duplexes using KOD DNA polymerase. Org. Biomol. Chem. 7, 1404-1409. DOI ScienceOn
31	Cai, W. and Chen, X. (2007) Nanoplatforms for targeted molecular imaging in living subjects. Small 3, 1840-1854. DOI ScienceOn
32	Berezovski, M., Drabovich, A., Krylova, S. M., Musheev, M., Okhonin, V., Petrov, A. and Krylov, S. N. (2005) Nonequilibrium capillary electrophoresis of equilibrium mixtures: a universal tool for development of aptamers. J. Am. Chem. Soc. 127, 3165-3171. DOI ScienceOn
33	Blank, M., Weinschenk, T., Priemer, M. and Schluesener, H. (2001) Systematic evolution of a DNA aptamer binding to rat brain tumor microvessels. selective targeting of endothelial regulatory protein pigpen. J. Biol. Chem. 276, 16464-16468. DOI ScienceOn
34	Bruno, J. G., Carrillo, M. P., Phillips, T., Vail, N. K. and Hanson, D. (2008) Competitive FRET-aptamer-based detection of methylphosphonic acid, a common nerve agent metabolite. J. Fluoresc. 18, 867-876. DOI
35	Chen, F., Hu, Y., Li, D., Chen, H. and Zhang, X. L. (2009) CS-SELEX generates high-affinity ssDNA aptamers as molecular probes for hepatitis C virus envelope glycoprotein E2. PLoS One 4, e8142 DOI ScienceOn
36	Chu, T. C., Marks, J. W. 3rd, Lavery, L. A., Faulkner, S., Rosenblum, M. G., Ellington, A. D. and Levy, M. (2006a) Aptamer:toxin conjugates that specifically target prostate tumor cells. Cancer Res. 66, 5989-5992. DOI ScienceOn
37	Chu, T. C., Twu, K. Y., Ellington, A. D. and Levy, M. (2006b) Aptamer mediated siRNA delivery. Nucleic Acids Res. 34, e73 DOI ScienceOn
38	Cox, J. C., Rudolph, P. and Ellington, A. D. (1998) Automated RNA selection. Biotechnol. Prog. 14, 845-850. DOI ScienceOn
39	Cui, Z. Q., Ren, Q., Wei, H. P., Chen, Z., Deng, J. Y., Zhang, Z. P. and Zhang, X. E. (2011) Quantum dot-aptamer nanoprobes for recognizing and labeling infl uenza A virus particles. Nanoscale. 3, 2454-2457. DOI ScienceOn
40	Wang, C. H., Huang, Y. F. and Yeh, C. K. (2011) Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging. Langmuir 27, 6971-6976. DOI ScienceOn
41	Wang, J., Jiang, H. and Liu, F. (2000) in vitro selection of novel RNA ligands that bind human cytomegalovirus and block viral infection. RNA 6, 571-583. DOI ScienceOn
42	White, R., Rusconi, C., Scardino, E., Wolberg, A., Lawson, J., Hoffman, M. and Sullenger, B. (2001) Generation of species crossreactive aptamers using "toggle" SELEX. Mol. Ther. 4, 567-573. DOI ScienceOn
43	Williams, K. P., Liu, X. H., Schumacher, T. N., Lin, H. Y., Ausiello, D. A., Kim, P. S. and Bartel, D. P. (1997) Bioactive and nuclease-resistant L-DNA ligand of vasopressin. Proc. Natl. Acad. Sci. U.S.A. 94, 11285-11290. DOI
44	Wittung, P., Nielsen, P. E., Buchardt, O., Egholm, M. and Norden, B. (1994) DNA-like double helix formed by peptide nucleic acid. Nature 368, 561-563. DOI ScienceOn
45	Wullner, U., Neef, I., Eller, A., Kleines, M., Tur, M. K. and 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, 554-565. DOI ScienceOn
46	Xu, W. and Lu, Y. (2011) A smart magnetic resonance imaging contrast agent responsive to adenosine based on a DNA aptamer-conjugated gadolinium complex. Chem. Commun. 47, 4998-5000. DOI ScienceOn
47	Yang, X., Fennewald, S., Luxon, B. A., Aronson, J., Herzog, N. K. and Gorenstein, D. G. (1999) Aptamers containing thymidine 3'-Ophosphorodithioates: synthesis and binding to nuclear factor- ${\kappa}$ B. Bioorg. Med. Chem. Lett. 9, 3357-3362. DOI ScienceOn
48	Yang, X., Huang, J., Wang, K., Li, W., Cui, L. and Li, X. (2011) Angiogenin-mediated photosensitizer-aptamer conjugate for photodynamic therapy. ChemMedChem 6, 1788-1780.
49	Dollins, C. M., Nair, S., Boczkowski, D., Lee, J., Layzer, J. M., Gilboa, E. and Sullenger, B. A. (2008) Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer. Chem. Biol. 15, 675-682. DOI ScienceOn
50	Diener, J. L., Daniel Lagasse, H. A., Duerschmied, D., Merhi, Y., Tanguay, J. F., Hutabarat, R., Gilbert, J., Wagner, D. D. and Schaub, R. (2009) Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779. J. Thromb. Haemost. 7, 1155-1162. DOI ScienceOn
51	Ellington, A. D. and Szostak, J. W. (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818-822. DOI ScienceOn
52	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. DOI
53	Floege, J., Ostendorf, T., Janssen, U., Burg, M., Radeke, H. H., Vargeese, C., Gill, S. C., Green, L. S. and Janjic, N. (1999) Novel approach to specific growth factor inhibition in vivo: antagonism of platelet-derived growth factor in glomerulonephritis by aptamers. Am. J. Pathol. 154, 169-179. DOI ScienceOn
54	Foy, J. W., Rittenhouse, K., Modi, M. and Patel, M. (2007) Local tolerance and systemic safety of pegaptanib sodium in the dog and rabbit. J. Ocul. Pharmacol. Ther. 23, 452-466. DOI ScienceOn
55	Gilboa, E., McNamara, J. 2nd and Pastor, F. (2013) Use of oligonucleotide aptamer ligands to modulate the function of immune receptors. Clin. Cancer Res. 19, 1054-1062. DOI ScienceOn
56	Gissel, M., Orfeo, T., Foley, J. H. and Butenas, S. (2012) Effect of BAX499 aptamer on tissue factor pathway inhibitor function and thrombin generation in models of hemophilia. Thromb. Res. 130, 948-955. DOI ScienceOn
57	Zhang, Y., Hong, H. and Cai W. (2011) Tumor-targeted drug delivery with aptamers. Curr. Med. Chem. 18, 4185-4194. DOI ScienceOn
58	Yigit, M. V., Mazumdar, D., Kim, H. K., Lee, J. H., Odintsov, B. and Lu, Y. (2007) Smart "turn-on" magnetic resonance contrast agents based on aptamer-functionalized superparamagnetic iron oxide nanoparticles. Chembiochem 8, 1675-1678. DOI ScienceOn
59	Zhang, C., Ji, X., Zhang, Y., Zhou, G., Ke, X., Wang, H., Tinnefeld, P. and He, Z. (2013) One-pot synthesized aptamer-functionalized CdTe: $Zn^{2+}$ quantum dots for tumor-targeted fl uorescence imaging in vitro and in vivo. Anal. Chem. 85, 5843-5849. DOI ScienceOn
60	Zhang, M. Z., Yu, R. N., Chen, J., Ma, Z. Y. and Zhao, Y. D. (2012) Targeted quantum dots fluorescence probes functionalized with aptamer and peptide for transferrin receptor on tumor cells. Nanotechnology 23, 485104. DOI ScienceOn
61	Zhou, B. and Wang, B. (2006) Pegaptanib for the treatment of agerelated macular degeneration. Exp. Eye Res. 83, 615-619. DOI ScienceOn
62	Zhou, J., Li, H., Li, S., Zaia, J. and Rossi, J. J. (2008) Novel dual inhibitory function aptamer-siRNA delivery system for HIV-1 therapy. Mol. Ther. 16, 1481-1489. DOI ScienceOn
63	Zhou, J., Li, H., Zhang, J., Piotr, S. and Rossi J. (2011a) Development of cell-type specific anti-HIV gp120 aptamers for siRNA delivery. J. Vis. Exp. 23, 2954.
64	Zhou, J., Neff, C. P., Swiderski, P., Li, H., Smith, D. D., Aboellail, T., Remling-Mulder, L., Akkina, R. and Rossi, J. J. (2013) Functional in vivo delivery of multiplexed anti-HIV-1 siRNAs via a chemically synthesized aptamer with a sticky bridge. Mol. Ther. 21, 192-200. DOI ScienceOn
65	Healy, J. M., Lewis, S. D., Kurz, M., Boomer, R. M., Thompson, K. M., Wilson, C. and McCauley, T. G. (2004) Pharmacokinetics and biodistribution of novel aptamer compositions. Pharm. Res. 21, 2234-2246. DOI
66	Gudima, S.O., Kostyuk, D. A., Grishchenko, O. I., Tunitskaya, V. L., Memelova, L. V. and Kochetkov, S. N. (1998) Synthesis of mixed ribo/deoxyribopolynucleotides by mutant T7 RNA polymerase. FEBS Lett. 439, 302-306. DOI ScienceOn
67	Hamula, C. L., Le, X. C. and Li, X. F. (2011) DNA aptamers binding to multiple prevalent M-types of Streptococcus pyogenes. Anal. Chem. 83, 3640-3647. DOI ScienceOn
68	Han, D., Zhu, G., Wu, C., Zhu, Z., Chen, T., Zhang, X. and Tan, W. (2013) Engineering a cell-surface aptamer circuit for targeted and amplified photodynamic cancer therapy. ACS Nano 7, 2312-2319. DOI ScienceOn
69	Hicke, B. J., Stephens, A. W., Gould, T., Chang, Y. F., Lynott, C. K., Heil, J., Borkowski, S., Hilger, C. S., Cook, G., Warren, S. and Schmidt, P. G. (2006) Tumor targeting by an aptamer. J. Nucl. Med. 47, 668-678.
70	Holahan, M. R., Madularu, D., McConnell, E. M., Walsh, R. and DeRosa, M. C. (2011) Intra-accumbens injection of a dopamine aptamer abates MK-801-induced cognitive dysfunction in a model of schizophrenia. PLoS One 6, e22239. DOI
71	Holland, C. A., Henry, A. T., Whinna, H. C. and Church, F. C. (2000) Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin. FEBS Lett. 484, 87-91. DOI ScienceOn
72	Hong, H., Goel, S., Zhang, Y. and Cai, W. (2011) Molecular imaging with nucleic acid aptamers. Curr. Med. Chem. 18, 4195-4205. DOI
73	Hooks, M. A., Wade, C. S. and Millikan, W. J. (1991) Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation. Pharmacotherapy 11, 26-37.
74	Hussain, A. F., Tur, M. K. and Barth, S. (2013) An aptamer-siRNA chimera silences the eukaryotic elongation factor 2 gene and induces apoptosis in cancers expressing ${\alpha}$ v ${\beta}$ 3 integrin. Nucleic Acid Ther. 23, 203-212. DOI
75	Zhou, J., Shu, Y., Guo, P., Smith, D. D. and Rossi, J. J. (2011b) Dual functional RNA nanoparticles containing phi29 motor pRNA and anti-gp120 aptamer for cell-type specific delivery and HIV-1 inhibition. Methods 54, 284-294. DOI ScienceOn
76	Zhu, G., Ye, M., Donovan, M. J., Song, E., Zhao, Z. and Tan, W. (2012A) Nucleic acid aptamers: an emerging frontier in cancer therapy. Chem. Commun. (Camb) 48, 10472-10480. DOI ScienceOn
77	Zhu, Q., Shibata, T., Kabashima, T. and Kai, M. (2012B) Inhibition of HIV-1 protease expression in T cells owing to DNA aptamer-mediated specific delivery of siRNA. Eur. J. Med. Chem. 56, 396-399. DOI ScienceOn
78	Horhota, A., Zou, K., Ichida, J. K., Yu, B., McLaughlin, L. W., Szostak, J. W. and Chaput, J. C. (2005) Kinetic analysis of an efficient DNAdependent TNA polymerase. J. Am. Chem. Soc. 127, 7427-7434. DOI ScienceOn
79	Huang, Y. F., Shangguan, D., Liu, H., Phillips, J. A., Zhang, X., Chen, Y. and Tan, W. (2009) Molecular assembly of an aptamer-drug conjugate for targeted drug delivery to tumor cells. Chembiochem. 10, 862-868. DOI ScienceOn
80	Hwang do, W., Ko, H. Y., Lee, J. H., Kang, H., Ryu, S. H., Song, I. C., Lee, D. S. and Kim, S. (2010) A nucleolin-targeted multimodal nanoparticle imaging probe for tracking cancer cells using an aptamer. J. Nucl. Med. 51, 98-105. DOI
81	Hybarger, G., Bynum, J., Williams, R. F., Valdes, J. J. and Chambers, J. P. (2006) A microfl uidic SELEX prototype. Anal. Bioanal. Chem. 384, 191-198. DOI
82	Ichida, J. K., Zou, K., Horhota, A., Yu, B., McLaughlin, L. W. and Szostak, J. W. (2005) An in vitro selection system for TNA. J. Am. Chem. Soc. 127, 2802-2803. DOI ScienceOn
83	Jayasena, S. D. (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin. Chem. 45, 1628-1650.
84	Jenison, R. D., Gill, S. C., Pardi, A. and Polisky, B. (1994) High-resolution molecular discrimination by RNA. Science 263, 1425-1429. DOI
85	Kasahara, Y. and Kuwahara, M. (2012) Artifi cial specific binders directly recovered from chemically modified nucleic Acid libraries. J. Nucleic Acids 2012, 156482.
86	Kim, D., Jeong, Y. Y. and Jon, S. (2010) A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano 4, 3689-3696. DOI ScienceOn
87	Kasahara, Y., Irisawa, Y., Ozaki, H., Obika, S. and Kuwahara, M. (2013) 2',4'-BNA/LNA aptamers: CE-SELEX using a DNA-based library of full-length 2'-O, 4'-C-methylene-bridged/linked bicyclic ribonucleotides. Bioorg. Med. Chem. Lett. 23, 1288-1292. DOI ScienceOn
88	Kawakami, J., Imanaka, H., Yokota, Y. and Sugimoto, N. (2000) in vitro selection of aptamers that act with $Zn^{2+}$ . J. Inorg. Biochem. 82, 197-206. DOI ScienceOn
89	Kempeneers, V., Renders, M., Froeyen, M. and Herdewijn, P. (2005) Investigation of the DNA-dependent cyclohexenyl nucleic acid polymerization and the cyclohexenyl nucleic acid-dependent DNA polymerization. Nucleic Acids Res. 33, 3828-3836. DOI ScienceOn
90	Kim, S., Kim, Y., Kim, P., Ha, J., Kim, K., Sohn, M., Yoo, J. S., Lee, J., Kwon, J. A. and Lee, K. N. (2006) Improved sensitivity and physical properties of sol-gel protein chips using large-scale material screening and selection. Anal. Chem. 78, 7392-7396. DOI ScienceOn
91	Klussmann, S., Nolte, A., Bald, R., Erdmann, V. A. and Furste, J. P. (1996) Mirror-image RNA that binds D-adenosine. Nat. Biotechnol. 14, 1112-1115. DOI ScienceOn
92	Knight, D. M., Trinh, H., Le, J., Siegel, S., Shealy, D., McDonough, M., Scallon, B., Moore, M. A., Vilcek, J. and Daddona, P. (1993) Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol. Immunol. 30, 1443-1453. DOI ScienceOn
93	Kolesnikova, O., Kazakova, H., Comte, C., Steinberg, S., Kamenski, P., Martin, R. P., Tarassov, I. and Entelis, N. (2010) Selection of RNA aptamers imported into yeast and human mitochondria. RNA 16, 926-941. DOI ScienceOn
94	Kuwahara, M., Takeshima, H., Nagashima, J., Minezaki, S., Ozaki, H. and Sawai, H. (2009) Transcription and reverse transcription of artifi cial nucleic acids involving backbone modifi cation by template directed DNA polymerase reactions. Bioorg. Med. Chem. 17, 3782-3788. DOI ScienceOn
95	Kuwahara, M., Obika, S., Nagashima, J., Ohta, Y., Suto, Y., Ozaki, H., Sawai, H. and Imanishi, T. (2008) Systematic analysis of enzymatic DNA polymerization using oligo-DNA templates and triphosphate analogs involving 2',4'-bridged nucleosides. Nucleic Acids Res. 36, 4257-4265. DOI ScienceOn
96	Kuwahara, M., Takahata, Y., Shoji, A., Ozaki, A. N., Ozaki, H. and Sawai, H. (2003) Substrate properties of C5-substituted pyrimidine 2'-deoxynucleoside 5'-triphosphates for thermostable DNA polymerases during PCR. Bioorg. Med. Chem. Lett. 13, 3735-3738. DOI ScienceOn
97	Kuwahara, M., Takano, Y., Kasahara, Y., Nara, H., Ozaki, H., Sawai, H., Sugiyama, A. and Obika, S. (2010) Study on suitability of KOD dna polymerase for enzymatic production of artifi cial nucleic acids using base/sugar modified nucleoside triphosphates. Molecules 15, 8229-8240. DOI ScienceOn
98	Latham, J. A., Johnson, R. and Toole, J. J. (1994) The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing 5-(1-pentynyl)-2'-deoxyuridine. Nucleic Acids Res. 22, 2817-2822. DOI ScienceOn
99	Lato, S. M., Ozerova, N. D., He, K. , Sergueeva, Z., Shaw, B. R. and Burke, D. H. (2002) Boron-containing aptamers to ATP. Nucleic Acids Res. 30, 1401-1407. DOI ScienceOn
100	Lauhon, C. T. and Szostak, J. W. (1995) RNA aptamers that bind flavin and nicotinamide redox cofactors. J. Am. Chem. Soc. 117, 1246-1257. DOI ScienceOn
101	Leal, N. A., Sukeda, M. and Benner, S. A. (2006) Dynamic assembly of primers on nucleic acid templates. Nucleic Acids Res. 34, 4702-4710. DOI ScienceOn
102	Liu, Z., Duan, J. H., Song, Y. M., Ma, J., Wang, F. D., Lu, X., Yang and X. D. (2012) Novel HER2 aptamer selectively delivers cytotoxic drug to HER2-positive breast cancer cells in vitro. J. Transl. Med. 10, 148. DOI
103	Leva, S., Lichte, A., Burmeister, J., Muhn, P., Jahnke, B., Fesser, D., Erfurth, J., Burgstaller, P. and Klussmann, S. (2002) GnRH binding RNA and DNA Spiegelmers: a novel approach toward GnRH antagonism. Chem. Biol. 9, 351-359. DOI ScienceOn
104	Li, F., Du, Z., Yang, L. and Tang, B. (2013) Selective and sensitive turnon detection of adenosine triphosphate and thrombin based on bifunctional fl uorescent oligonucleotide probe. Biosens. Bioelectron. 41, 907-910. DOI ScienceOn
105	Li, M., Lin, N., Huang, Z., Du, L., Altier, C., Fang, H. and Wang, B. (2008) Selecting aptamers for a glycoprotein through the incorporation of the boronic acid moiety. J. Am. Chem. Soc. 130, 12636-12638. DOI ScienceOn
106	Lou, X., Qian, J., Xiao, Y., Viel, L., Gerdon, A. E., Lagally, E. T., Atzberger, P., Tarasow, T. M., Heeger, A. J. and Soh, H. T. (2009) Micromagnetic selection of aptamers in microfl uidic channels. Proc. Natl. Acad. Sci. U.S.A 106, 2989-2994. DOI ScienceOn
107	Mann, A. P., Bhavane, R. C., Somasunderam, A., Liz Montalvo-Ortiz, B., Ghaghada, K. B., Volk, D., Nieves-Alicea, R., Suh, K. S., Ferrari, M., Annapragada, A., Gorenstein, D. G. and Tanaka, T. (2011) Thioaptamer conjugated liposomes for tumor vasculature targeting. Oncotarget 2, 298-304.
108	Mann, D., Reinemann, C., Stoltenburg, R. and Strehlitz, B. (2005) in vitro selection of DNA aptamers binding ethanolamine. Biochem. Biophys. Res. Commun. 338, 1928-1934. DOI ScienceOn
109	Maul, T. M., Dudgeon, D. D., Beste, M. T., Hammer, D. A., Lazo, J. S., Villanueva, F. S. and Wagner, W. R. (2010) Optimization of ultrasound contrast agents with computational models to improve selection of ligands and binding strength. Biotechnol. Bioeng. 107, 854-864. DOI ScienceOn
110	Mazumdar, S. and Greenwald, D. (2009) Golimumab. MAbs 1, 422-431. DOI
111	McIntyre, J. O. and Matrisian, L. M. (2003) Molecular imaging of proteolytic activity in cancer. J. Cell. Biochem. 90, 1087-1097. DOI ScienceOn
112	McNamara, J. O. 2nd, Andrechek, E. R., Wang, Y., Viles, K. D., Rempel, R. E., Gilboa, E., Sullenger, B. A. and Giangrande, P. H. (2006) Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat. Biotechnol. 24, 1005-1015. DOI ScienceOn
113	McNamara, J. O., Kolonias, D., Pastor, F., Mittler, R. S., Chen, L., Giangrande, P. H., Sullenger, B. and Gilboa, E. (2008) Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J. Clin. Invest. 118, 376-386. DOI ScienceOn
114	Meng, L., Yang, L., Zhao, X., Zhang, L., Zhu, H., Liu, C. and Tan, W. (2012) Targeted delivery of chemotherapy agents using a liver cancer-specific aptamer. PLoS One 7, e33434. DOI
115	Mi, J., Liu, Y., Rabbani, Z. N., Yang, Z., Urban, J. H., Sullenger, B. A. and Clary, B. M. (2010) in vivo selection of tumor-targeting RNA motifs. Nat. Chem. Biol. 6, 22-24. DOI ScienceOn
116	Mosing, R. K., Mendonsa, S. D. and Bowser, M. T. (2005) Capillary electrophoresis-SELEX selection of aptamers with affinity for HIV-1 reverse transcriptase. Anal. Chem. 77, 6107-6112. DOI ScienceOn
117	Neff, C. P., Zhou, J., Remling, L., Kuruvilla, J., Zhang, J., Li, H., Smith, D. D., Swiderski, P., Rossi, J. J. and Akkina, R. (2011) An aptamersiRNA chimera suppresses HIV-1 viral loads and protects from helper CD4(+) T cell decline in humanized mice. Sci. Transl. Med. 3, 66ra6.
118	Nitsche, A., Kurth, A., Dunkhorst, A., Panke, O., Sielaff, H., Junge, W., Muth, D., Scheller, F., Stocklein, W., Dahmen, C., Pauli, G. and Kage, A. (2007) One-step selection of Vaccinia virus-binding DNA aptamers by MonoLEX. BMC Biotechnol. 7, 48. DOI

Reference

1	Nik Nik Kamarudin. (2017) Biomedicines Aptamer Technology: Adjunct Therapy for Malaria / 5 (1) , 1
9	Ruth Roder. (2014) Therapeutic Delivery Sequence-defined shuttles for targeted nucleic acid and protein delivery / 5 (9) , 1025
	X. Zheng. (2015) Toxicon A saxitoxin-binding aptamer with higher affinity and inhibitory activity optimized by rational site-directed mutagenesis and truncation / 101 , 41
1	Joline Tung. (2017) Scientific Reports A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative Breast Cancer Cells within 24 hours / 7 (1)
1	Tarek Mohamed Abd El-Aziz. (2017) Scientific Reports Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides / 7 (1)
	Christina Greenwood. (2015) Biomolecular Detection and Quantification Proximity assays for sensitive quantification of proteins / 4 , 10
4	John Bruno. (2015) Molecules Predicting the Uncertain Future of Aptamer-Based Diagnostics and Therapeutics / 20 (4) , 6866
	N. Ardjomandi. (2016) Materials Science and Engineering: C Surface biofunctionalization of β-TCP blocks using aptamer 74 for bone tissue engineering / 67 , 267
10	Feng Jiang. (2015) International Journal of Molecular Sciences Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems / 16 (10) , 23784
8	Lukas J. Aaldering. (2017) ChemBioChem Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule / 18 (8) , 755
3	Sven Kruspe. (2017) Biomedicines Aptamer-siRNA Chimeras: Discovery, Progress, and Future Prospects / 5 (3) , 45
	Xiaoping Hu. (2015) International Journal of Molecular Medicine Ras ssDNA aptamer inhibits vascular smooth muscle cell proliferation and migration through MAPK and PI3K pathways /
17	Shunxiang Gao. (2016) Analytical and Bioanalytical Chemistry Post-SELEX optimization of aptamers / 408 (17) , 4567
3	(2017) Biomedicines Development of Phosphorothioate DNA and DNA Thioaptamers / 5 (3) , 41
	Keith E Maier. (2016) Molecular Therapy - Methods & Clinical Development From selection hits to clinical leads: progress in aptamer discovery / 3 , 16014
4	Chin-Yu Wang. (2016) International Journal of Cancer An aptamer targeting shared tumor-specific peptide antigen of MAGE-A3 in multiple cancers / 138 (4) , 918
1	Соловаров. (2017) Бюллетень Восточно-Сибирского научного центра Сибирского отделения Российской академии медицинских наук ASSESSMENT OF NEUTRALIZING PROPERTIES OF DNA-APTAMERS AND EXTRACTS OF MEDICINAL HERBS AGAINST THE TICK-BORNE ENCEPHALITIS VIRUS / 2 (1) , 84
1	Katherine Perschbacher. (2015) Nucleic Acid Therapeutics Quantitative PCR Analysis of DNA Aptamer Pharmacokinetics in Mice / 25 (1) , 11
	Yinze Zhang. (2015) Analytical Biochemistry Indirect purification method provides high yield and quality ssDNA sublibrary for potential aptamer selection / 476 , 84
1	Ken-ichiro Matsunaga. (2016) Scientific Reports Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications / 5 (1)
	Alexey V. Samokhvalov. (2017) Analytica Chimica Acta Use of anchor protein modules in fluorescence polarisation aptamer assay for ochratoxin A determination / 962 , 80
4	Weibin Li. (2015) Nucleic Acid Therapeutics Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune Disease / 25 (4) , 173
	Xiaoqian Wang. (2017) Journal of Chromatography A Multiple modes of capillary electrophoresis applied in peptide nucleic acid related study / 1501 , 161
31	Gonca Bulbul. (2015) Nanoscale A generic amplification strategy for electrochemical aptasensors using a non-enzymatic nanoceria tag / 7 (31) , 13230
	Syed Faaiz Enam. (2017) Biomaterials Enrichment of endogenous fractalkine and anti-inflammatory cells via aptamer-functionalized hydrogels / 142 , 52
4	E. Suaebah. (2017) Journal of Applied Physics Aptamer strategy for ATP detection on nanocrystalline diamond functionalized by a nitrogen and hydrogen radical beam system / 121 (4) , 044506
4	Wei Fan. (2016) Journal of Drug Targeting Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo / 24 (4) , 359
1	Christopher Oelkrug. (2015) Journal of Cellular and Molecular Medicine Antibody- and aptamer-strategies for GvHD prevention / 19 (1) , 11
	María A. Dellafiore. (2016) Frontiers in Chemistry Modified Nucleoside Triphosphates for In-vitro Selection Techniques / 4
8	Katherine Groff. (2015) Biotechnology Advances Modern affinity reagents: Recombinant antibodies and aptamers / 33 (8) , 1787
8	Eric Ouellet. (2015) Biotechnology and Bioengineering Hi-Fi SELEX: A high-fidelity digital-PCR based therapeutic aptamer discovery platform / 112 (8) , 1506
2	Phat-Loc Nguyen. (2017) Toxicology and Environmental Health Sciences Aptasensor for environmental monitoring / 9 (2) , 89
	Emma Goux. (2016) Methods Fluorescence anisotropy-based structure-switching aptamer assay using a peptide nucleic acid (PNA) probe / 97 , 69
4	Ji Won Lee. (2015) BMB Reports Therapeutic aptamers: developmental potential as anticancer drugs / 48 (4) , 234
	Jin Her. (2017) Sensors and Actuators B: Chemical Enzyme-linked antibody aptamer assays based colorimetric detection of soluble fraction of activated leukocyte cell adhesion molecule / 242 , 529
17	Jing Zhao. (2015) The Analyst Analysis of ATP and AMP binding to a DNA aptamer and its imidazole-tethered derivatives by surface plasmon resonance / 140 (17) , 5881
5	Jiehua Xu. (2015) PLOS ONE Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX / 10 (5) , e0125863
21	Emma Goux. (2015) Analytical and Bioanalytical Chemistry An improved design of the kissing complex-based aptasensor for the detection of adenosine / 407 (21) , 6515
22	A. Virgilio. (2015) Nucleic Acids Research Site-specific replacement of the thymine methyl group by fluorine in thrombin binding aptamer significantly improves structural stability and anticoagulant activity / 43 (22) , 10602
4	Nam Nguyen Quang. (2016) Pharmaceuticals Applications of High-Throughput Sequencing for In Vitro Selection and Characterization of Aptamers / 9 (4) , 76
11	Mawethu Bilibana. (2016) Sensors Electrochemical Aptatoxisensor Responses on Nanocomposites Containing Electro-Deposited Silver Nanoparticles on Poly(Propyleneimine) Dendrimer for the Detection of Microcystin-LR in Freshwater / 16 (11) , 1901
None	(2017) Journal of nucleic acids Aptamers as the Agent in Decontamination Assays (Apta-Decontamination Assays): From the Environment to the Potential Application <I> In Vivo</I> / 2017 (None) , 3712070
4	(2015) Antimicrobial Agents and Chemotherapy Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist / 59 (4) , 2072
2	(2017) Nature Chemical Biology Human antibody-based chemically induced dimerizers for cell therapeutic applications / 14 (2) , 112
6	(2018) BioTechniques in platelet concentrates / 65 (6) , 331
12	(2018) Genes Advances on Aptamers against Protozoan Parasites / 9 (12) , 584
10	(2018) Microchimica Acta SERS based aptasensor for ochratoxin A by combining Fe3O4@Au magnetic nanoparticles and Au-DTNB@Ag nanoprobes with multiple signal enhancement / 185 (10)
4	(2018) Pharmaceuticals Molecular Application of Aptamers in the Diagnosis and Treatment of Cancer and Communicable Diseases / 11 (4) , 93
01730835	(2019) ELECTROPHORESIS Peptide nucleic acid and amino acid modified peptide nucleic acid analysis by capillary zone electrophoresis / (01730835)
2	(2013) Journal of microbiology and biotechnology Emerging Frontiers of Graphene in Biomedicine / 25 (2) , 145
None	(2013) Scientific reports <I>In vitro</I> selections of mammaglobin A and mammaglobin B aptamers for the recognition of circulating breast tumor cells / 7 (None) , 14487
7	(2013) Analytical chemistry / Edit by American Chemical Society Panoply of Fluorescence Polarization/Anisotropy Signaling Mechanisms for Functional Nucleic Acid-Based Sensing Platforms / 90 (7) , 4236
15	(2013) Analytical chemistry / Edit by American Chemical Society Measurement of (Aptamer-Small Target) <I>K</I><SUB>D</SUB> Using the Competition between Fluorescently Labeled and Unlabeled Targets and the Detection of Fluorescence Anisotropy / 90 (15) , 9189
40	(2013) ACS applied materials & interfaces Cascaded Aptamers-Governed Multistage Drug-Delivery System Based on Biodegradable Envelope-Type Nanovehicle for Targeted Therapy of HER2-Overexpressing Breast Cancer / 10 (40) , 34050
3	(2013) Clinical chemistry Improved Detection of HER2 by a Quasi-Targeted Proteomics Approach Using Aptamer–Peptide Probe and Liquid Chromatography–Tandem Mass Spectrometry / 64 (3) , 526
10	(2019) Mini reviews in medicinal chemistry Aptamer Oligonucleotides as Potential Therapeutics in Hematologic Diseases / 19 (10) , 788
1	(2013) Pharmaceuticals Radiolabelled Aptamers for Theranostic Treatment of Cancer / 12 (1) , 2
10	(2019) International journal of molecular sciences Updates on Aptamer Research / 20 (10) , 2511
10	(2013) Molecules Recent Advances in Degradable Hybrids of Biomolecules and NGs for Targeted Delivery / 24 (10) , 1873
7	(2013) Nanotechnologies in Russia Application of Gold Nanoparticles for High-Sensitivity Fluorescence Polarization Aptamer Assay for Ochratoxin A / 14 (7) , 397
9	(2019) Bioconjugate chemistry Facile and Efficient Chemoenzymatic Semisynthesis of Fc-Fusion Compounds for Half-Life Extension of Pharmaceutical Components / 30 (9) , 2323
None	(2013) Frontiers in pharmacology Internalized Functional DNA Aptamers as Alternative Cancer Therapies / 11 (None) , 1115
4	(2020) Photochemical & photobiological sciences : an international journal Conjugating biomaterials with photosensitizers: advances and perspectives for photodynamic antimicrobial chemotherapy / 19 (4) , 445
5	(2020) Acs applied bio materials Chemically Modified Aptamers in Biological Analysis / 3 (5) , 2816
2	(2020) Biotechnology & genetic engineering reviews Report on biopharmaceutical profile of recent biotherapeutics and insilco docking studies on target bindings of known aptamer biotherapeutics / 36 (2) , 57
5	(2013) Photochemistry and photobiology The Ca <SUP>2+</SUP> ‐Regulated Photoprotein Obelin as a Tool for SELEX Monitoring and DNA Aptamer Affinity Evaluation / 96 (5) , 1041
10	(2013) Cancers Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology / 12 (10) , 2889
1	(2013) Molecules Binding Characteristics Study of DNA based Aptamers for <I>E. coli</I> O157:H7 / 26 (1) , 204
1	(2021) Journal of medicinal chemistry Improving Thermodynamic Stability and Anticoagulant Activity of a Thrombin Binding Aptamer by Incorporation of 8-trifluoromethyl-2′-deoxyguanosine / 64 (1) , 711
None	(2021) Frontiers in cell and developmental biology Targeting Strategies for Enhancing Paclitaxel Specificity in Chemotherapy / 9 (None) , 626910
3	(2021) Life Recent Progress and Opportunities for Nucleic Acid Aptamers / 11 (3) , 193
8	(2013) ACS applied materials & interfaces Recent Progress in Aptamer Discoveries and Modifications for Therapeutic Applications / 13 (8) , 9500
8	(2013) ACS applied materials & interfaces Rationally Designed Multivalent Aptamers Targeting Cell Surface for Biomedical Applications / 13 (8) , 9369
7	(2021) International journal of molecular sciences Artificial Intelligence in Aptamer-Target Binding Prediction / 22 (7) , 3605
3	(2021) Biotechnology progress <SMALL>ANTI‐</SMALL> epithelial cell adhesion molecule <SMALL>RNA</SMALL> aptamer‐conjugated liposomal doxorubicin as an efficient targeted therapy in mice bearing colon carcinoma tumor / 37 (3) , None
6	(2021) Microchimica acta In situ food-borne pathogen sensors in a nanoconfined space by surface enhanced Raman scattering / 188 (6) , 201
6	(2013) Cells Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis / 10 (6) , 1455
34	(2013) New journal of chemistry Electrochemical aptasensors for the detection of hepatocellular carcinoma-related biomarkers / 45 (34) , 15158
None	(2013) Computational biology and chemistry In silico screening of ssDNA aptamer against Escherichia coli O157:H7: A machine learning and the Pseudo K-tuple nucleotide composition based approach / 95 (None) , 107568
None	(2013) Journal of controlled release : official journal of the Controlled Release Society Aptamer-mediated doxorubicin delivery reduces HCC burden in 3D organoids model / 341 (None) , 341