Generic placeholder image

Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Mini-Review Article

Current Status and Challenges of Aptamers Screening and Optimization

Author(s): Yong Tan, Lan Ma*, Xue Yang, Qi-Ni Cheng and Jiang-Feng Wu

Volume 26, Issue 6, 2023

Published on: 27 October, 2022

Page: [1067 - 1082] Pages: 16

DOI: 10.2174/1386207325666220501170846

Price: $65


Background: Aptamers, consisting of single-stranded DNA or RNA, have secondary and tertiary structures which could bind specifically to target molecules. They are characterized by strong specificity, high affinity, low molecular weight, and low immunogenicity; therefore, the current research focuses on their potential as a targeted drug carrier, a diagnostic probe for diseases, or as a direct therapeutic drug.

Objective: In this review, how to improve the success rate of adaptor screening and the optimization after screening is described.

Results: For aptamer screening, an efficient selection strategy is needed. In this article, by analyzing key aspects of SELEX such as initial library design, screening procedures, truncation and modification after screening, a comprehensive analysis of each step that might meet obstacles in SELEX is provided.

Conclusion: Aptamers, which possess the specificity and affinity with the target, can serve as targeted drug carriers or biosensors for diagnosing a disease. If the problems in the screening process in cell-SELEX technology, truncation, and modification after screening are solved, it will have a broader range of applications.

Keywords: Aptamer, SELEX, immunogenicity, antibodies, truncation, optimization.

Next »
Graphical Abstract
Ellington, A.D.; Szostak, J.W. In vitro selection of RNA molecules that bind specific ligands. Nature, 1990, 346(6287), 818-822.
[] [PMID: 1697402]
Tuerk, C.; Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science, 1990, 249(4968), 505-510.
[] [PMID: 2200121]
Pal, S.; Harmsen, S.; Oseledchyk, A.; Hsu, H.T.; Kircher, M.F. MUC1 aptamer targeted SERS nanoprobes. Adv. Funct. Mater., 2017, 27(32), 1606632.
[] [PMID: 29147108]
Ireson, C.R.; Kelland, L.R. Discovery and development of anticancer aptamers. Mol. Cancer Ther., 2006, 5(12), 2957-2962.
[] [PMID: 17172400]
Ye, M.; Hu, J.; Peng, M.; Liu, J.; Liu, J.; Liu, H.; Zhao, X.; Tan, W. Generating aptamers by cell-SELEX for applications in molecular medicine. Int. J. Mol. Sci., 2012, 13(3), 3341-3353.
[] [PMID: 22489154]
Diafa, S.; Hollenstein, M. Generation of aptamers with an expanded chemical repertoire. Molecules, 2015, 20(9), 16643-16671.
[] [PMID: 26389865]
Ng, E.W.M.; Adamis, A.P. Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases. Ann. N. Y. Acad. Sci., 2006, 1082(1), 151-171.
[] [PMID: 17145936]
Ferrara, N.; Damico, L.; Shams, N.; Lowman, H.; Kim, R. Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina, 2006, 26(8), 859-870.
[] [PMID: 17031284]
Friberg, T.R.; Tolentino, M.; Weber, P.; Patel, S.; Campbell, S.; Goldbaum, M. Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: The LEVEL study. Br. J. Ophthalmol., 2010, 94(12), 1611-1617.
[] [PMID: 20472746]
Tuñón, J.; Ruiz-Moreno, J.M.; Martín-Ventura, J.L.; Blanco-Colio, L.M.; Lorenzo, O.; Egido, J. Cardiovascular risk and antiangiogenic therapy for age-related macular degeneration. Surv. Ophthalmol., 2009, 54(3), 339-348.
[] [PMID: 19422962]
Lao, Y.H.; Phua, K.K.L.; Leong, K.W. Aptamer nanomedicine for cancer therapeutics: Barriers and potential for translation. ACS Nano, 2015, 9(3), 2235-2254.
[] [PMID: 25731717]
Hamada, M. In silico approaches to RNA aptamer design. Biochimie, 2018, 145, 8-14.
[] [PMID: 29032056]
Darmostuk, M.; Rimpelova, S.; Gbelcova, H.; Ruml, T. Current approaches in SELEX: An update to aptamer selection technology. Biotechnol. Adv., 2015, 33(6), 1141-1161.
[] [PMID: 25708387]
Lin, H.; Zhang, W.; Jia, S.; Guan, Z.; Yang, C.J.; Zhu, Z. Microfluidic approaches to rapid and efficient aptamer selection. Biomicrofluidics, 2014, 8(4), 041501.
[] [PMID: 25379085]
Keefe, A.D.; Cload, S.T. SELEX with modified nucleotides. Curr. Opin. Chem. Biol., 2008, 12(4), 448-456.
[] [PMID: 18644461]
Bruno, J. A review of therapeutic aptamer conjugates with emphasis on new approaches. Pharmaceuticals (Basel), 2013, 6(3), 340-357.
[] [PMID: 24276022]
Thiel, W.H.; Bair, T.; Wyatt Thiel, K.; Dassie, J.P.; Rockey, W.M.; Howell, C.A.; Liu, X.Y.; Dupuy, A.J.; Huang, L.; Owczarzy, R.; Behlke, M.A.; McNamara, J.O., II; Giangrande, P.H. Nucleotide bias observed with a short SELEX RNA aptamer library. Nucleic Acid Ther., 2011, 21(4), 253-263.
[] [PMID: 21793789]
Li, L.; Xu, S.; Yan, H.; Li, X.; Yazd, H.S.; Li, X.; Huang, T.; Cui, C.; Jiang, J.; Tan, W. Nucleic acid aptamers for molecular diagnostics and therapeutics: Advances and perspectives. Angew. Chem. Int. Ed., 2021, 60(5), 2221-2231.
[] [PMID: 32282107]
Crouzier, L.; Dubois, C.; Edwards, S.L.; Lauridsen, L.H.; Wengel, J.; Veedu, R.N. Efficient reverse transcription using locked nucleic acid nucleotides towards the evolution of nuclease resistant RNA aptamers. PLoS One, 2012, 7(4), e35990.
[] [PMID: 22558297]
Lee, I.; Berdis, A.J. Non-natural nucleotides as probes for the mechanism and fidelity of DNA polymerases. Biochim. Biophys. Acta. Proteins Proteomics, 2010, 1804(5), 1064-1080.
[] [PMID: 19733263]
Lipi, F.; Chen, S.; Chakravarthy, M.; Rakesh, S.; Veedu, R.N. In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies. RNA Biol., 2016, 13(12), 1232-1245.
[] [PMID: 27715478]
Liu, M.; Yin, Q.; Chang, Y.; Zhang, Q.; Brennan, J.D.; Li, Y. In vitro selection of circular DNA aptamers for biosensing applications. Angew. Chem. Int. Ed., 2019, 58(24), 8013-8017.
[] [PMID: 31020784]
Catuogno, S.; Esposito, C.L. Aptamer cell-based selection: Overview and advances. Biomedicines, 2017, 5(4), 49.
[] [PMID: 28805744]
Cowperthwaite, M.C.; Ellington, A.D. Bioinformatic analysis of the contribution of primer sequences to aptamer structures. J. Mol. Evol., 2008, 67(1), 95-102.
[] [PMID: 18594898]
Pan, W.; Clawson, G. The shorter the better: Reducing fixed primer regions of oligonucleotide libraries for aptamer selection. Molecules, 2009, 14(4), 1353-1369.
[] [PMID: 19384268]
Shtatland, T.; Gill, S.C.; Javornik, B.E.; Johansson, H.E.; Singer, B.S.; Uhlenbeck, O.C.; Zichi, D.A.; Gold, L. Interactions of Escherichia coli RNA with bacteriophage MS2 coat protein: Genomic SELEX. Nucleic Acids Res., 2000, 28(21), 93e-93.
[] [PMID: 11058143]
Djordjevic, M. SELEX experiments: New prospects, applications and data analysis in inferring regulatory pathways. Biomol. Eng., 2007, 24(2), 179-189.
[] [PMID: 17428731]
Kang, J.; Soog Lee, M.; Gorenstein, D.G. The enhancement of PCR amplification of a random sequence DNA library by DMSO and betaine: Application to in vitro combinatorial selection of aptamers. J. Biochem. Biophys. Methods, 2005, 64(2), 147-151.
[] [PMID: 16009429]
Wang, J.; Rudzinski, J.F.; Gong, Q.; Soh, H.T.; Atzberger, P.J. Influence of target concentration and background binding on in vitro selection of affinity reagents. PLoS One, 2012, 7(8), e43940.
[] [PMID: 22952815]
Banerjee, J.; Nilsen-Hamilton, M. Aptamers: Multifunctional molecules for biomedical research. J. Mol. Med. (Berl.), 2013, 91(12), 1333-1342.
[] [PMID: 24045702]
Gotrik, M.R.; Feagin, T.A.; Csordas, A.T.; Nakamoto, M.A.; Soh, H.T. Advancements in Aptamer discovery technologies. Acc. Chem. Res., 2016, 49(9), 1903-1910.
[] [PMID: 27526193]
Musheev, M.U.; Krylov, S.N. Selection of aptamers by systematic evolution of ligands by exponential enrichment: Addressing the polymerase chain reaction issue. Anal. Chim. Acta, 2006, 564(1), 91-96.
[] [PMID: 17723366]
Zhou, J.; Rossi, J. Erratum: Aptamers as targeted therapeutics: Current potential and challenges. Nat. Rev. Drug Discov., 2017, 16(6), 440.
[] [PMID: 28450742]
Kim, J.W.; Kim, E.Y.; Kim, S.Y.; Byun, S.K.; Lee, D.; Oh, K.J.; Kim, W.K.; Han, B.S.; Chi, S.W.; Lee, S.C.; Bae, K.H. Identification of DNA aptamers toward epithelial cell adhesion molecule via cell-SELEX. Mol. Cells, 2014, 37(10), 742-746.
[] [PMID: 25266702]
Tawiah, K.; Porciani, D.; Burke, D. Toward the selection of cell targeting Aptamers with extended biological functionalities to facilitate endosomal escape of cargoes. Biomedicines, 2017, 5(4), 51.
[] [PMID: 28837119]
Tan, S.Y.; Acquah, C.; Sidhu, A.; Ongkudon, C.M.; Yon, L.S.; Danquah, M.K. SELEX modifications and bioanalytical techniques for Aptamer–target binding characterization. Crit. Rev. Anal. Chem., 2016, 46(6), 521-537.
[] [PMID: 26980177]
Kuai, H.; Zhao, Z.; Mo, L.; Liu, H.; Hu, X.; Fu, T.; Zhang, X.; Tan, W. Circular bivalent Aptamers enable in vivo stability and recognition. J. Am. Chem. Soc., 2017, 139(27), 9128-9131.
[] [PMID: 28635257]
Byun, J. Recent progress and opportunities for nucleic acid aptamers. Life (Basel), 2021, 11(3), 193.
[] [PMID: 33671039]
Zhu, C.; Li, L.; Fang, S.; Zhao, Y.; Zhao, L.; Yang, G.; Qu, F. Selection and characterization of an ssDNA aptamer against thyroglobulin. Talanta, 2021, 223(Pt 1), 121690.
[] [PMID: 33303143]
Röthlisberger, P.; Hollenstein, M. Aptamer chemistry. Adv. Drug Deliv. Rev., 2018, 134, 3-21.
[] [PMID: 29626546]
McKeague, M.; McConnell, E.M.; Cruz-Toledo, J.; Bernard, E.D.; Pach, A.; Mastronardi, E.; Zhang, X.; Beking, M.; Francis, T.; Giamberardino, A.; Cabecinha, A.; Ruscito, A.; Aranda-Rodriguez, R.; Dumontier, M.; DeRosa, M.C. Analysis of in vitro aptamer selection parameters. J. Mol. Evol., 2015, 81(5-6), 150-161.
[] [PMID: 26530075]
Liu, J.; You, M.; Pu, Y.; Liu, H.; Ye, M.; Tan, W. Recent developments in protein and cell-targeted aptamer selection and applications. Curr. Med. Chem., 2011, 18(27), 4117-4125.
[] [PMID: 21838693]
Zhang, H.; Wang, Z.; Xie, L.; Zhang, Y.; Deng, T.; Li, J.; Liu, J.; Xiong, W.; Zhang, L.; Zhang, L.; Peng, B.; He, L.; Ye, M.; Hu, X.; Tan, W. Molecular recognition and in-vitro-targeted inhibition of renal cell carcinoma using a DNA Aptamer. Mol. Ther. Nucleic Acids, 2018, 12, 758-768.
[] [PMID: 30141409]
Lyu, Y.; Chen, G.; Shangguan, D.; Zhang, L.; Wan, S.; Wu, Y.; Zhang, H.; Duan, L.; Liu, C.; You, M.; Wang, J.; Tan, W. Generating cell targeting Aptamers for nanotheranostics using cell-SELEX. Theranostics, 2016, 6(9), 1440-1452.
[] [PMID: 27375791]
Sefah, K.; Shangguan, D.; Xiong, X.; O’Donoghue, M.B.; Tan, W. Development of DNA aptamers using Cell-SELEX. Nat. Protoc., 2010, 5(6), 1169-1185.
[] [PMID: 20539292]
Zhu, G.; Meng, L.; Ye, M.; Yang, L.; Sefah, K.; O’Donoghue, M.B.; Chen, Y.; Xiong, X.; Huang, J.; Song, E.; Tan, W. Self-assembled aptamer-based drug carriers for bispecific cytotoxicity to cancer cells. Chem. Asian J., 2012, 7(7), 1630-1636.
[] [PMID: 22492537]
Suzuki, Y.; Liu, S.; Ogasawara, T.; Sawasaki, T.; Takasaki, Y.; Yorozuya, T.; Mogi, M. A novel MRGPRX2-targeting antagonistic DNA aptamer inhibits histamine release and prevents mast cell-mediated anaphylaxis. Eur. J. Pharmacol., 2020, 878, 173104.
[] [PMID: 32320700]
Bruno, J.G.; Kiel, J.L. In vitro selection of DNA aptamers to anthrax spores with electrochemiluminescence detection. Biosens. Bioelectron., 1999, 14(5), 457-464.
[] [PMID: 10451913]
Paul, A.; Avci-Adali, M.; Ziemer, G.; Wendel, H.P. Streptavidin-coated magnetic beads for DNA strand separation implicate a multitude of problems during cell-SELEX. Oligonucleotides, 2009, 19(3), 243-254.
[] [PMID: 19732022]
Xuan, W.; Peng, Y.; Deng, Z.; Peng, T.; Kuai, H.; Li, Y.; He, J.; Jin, C.; Liu, Y.; Wang, R.; Tan, W. A basic insight into aptamer-drug conjugates (ApDCs). Biomaterials, 2018, 182, 216-226.
[] [PMID: 30138784]
Gao, S.; Zheng, X.; Jiao, B.; Wang, L. Post-SELEX optimization of aptamers. Anal. Bioanal. Chem., 2016, 408(17), 4567-4573.
[] [PMID: 27173394]
Liu, Y.; Le, C.; Tyrrell, D.L.; Le, X.C.; Li, X.F. Aptamer binding assay for the E Antigen of Hepatitis B using modified Aptamers with G-Quadruplex structures. Anal. Chem., 2020, 92(9), 6495-6501.
[] [PMID: 32250595]
Shangguan, D.; Tang, Z.; Mallikaratchy, P.; Xiao, Z.; Tan, W. Optimization and modifications of aptamers selected from live cancer cell lines. ChemBioChem, 2007, 8(6), 603-606.
[] [PMID: 17373017]
Tao, X.; He, F.; Liu, X.; Zhang, F.; Wang, X.; Peng, Y.; Liu, J. Detection of chloramphenicol with an aptamer-based colorimetric assay: Critical evaluation of specific and unspecific binding of analyte molecules. Mikrochim. Acta, 2020, 187(12), 668.
[] [PMID: 33215333]
Bavi, R.; Hang, Z.; Banerjee, P.; Aquib, M.; Jadhao, M.; Rane, N.; Bavi, S.; Bhosale, R.; Kodam, K.; Jeon, B.H.; Gu, Y. Doxorubicin-conjugated innovative 16-mer DNA Aptamer-Based Annexin A1 targeted anti-cancer drug delivery. Mol. Ther. Nucleic Acids, 2020, 21, 1074-1086.
[] [PMID: 32854062]
Wei, H.; Cai, R.; Yue, H.; Tian, Y.; Zhou, N. Screening and application of a truncated aptamer for high-sensitive fluorescent detection of metronidazole. Anal. Chim. Acta, 2020, 1128, 203-210.
[] [PMID: 32825904]
Mallikaratchy, P.R.; Ruggiero, A.; Gardner, J.R.; Kuryavyi, V.; Maguire, W.F.; Heaney, M.L.; McDevitt, M.R.; Patel, D.J.; Scheinberg, D.A. A multivalent DNA aptamer specific for the B-cell receptor on human lymphoma and leukemia. Nucleic Acids Res., 2011, 39(6), 2458-2469.
[] [PMID: 21030439]
Lupold, S.E.; Hicke, B.J.; Lin, Y.; Coffey, D.S. Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res., 2002, 62(14), 4029-4033.
[PMID: 12124337]
Chen, Z.; Liu, H.; Jain, A.; Zhang, L.; Liu, C.; Cheng, K. Discovery of Aptamer ligands for hepatic stellate cells using SELEX. Theranostics, 2017, 7(12), 2982-2995.
[] [PMID: 28839458]
Gold, L.; Ayers, D.; Bertino, J.; Bock, C.; Bock, A.; Brody, E.N.; Carter, J.; Dalby, A.B.; Eaton, B.E.; Fitzwater, T.; Flather, D.; Forbes, A.; Foreman, T.; Fowler, C.; Gawande, B.; Goss, M.; Gunn, M.; Gupta, S.; Halladay, D.; Heil, J.; Heilig, J.; Hicke, B.; Husar, G.; Janjic, N.; Jarvis, T.; Jennings, S.; Katilius, E.; Keeney, T.R.; Kim, N.; Koch, T.H.; Kraemer, S.; Kroiss, L.; Le, N.; Levine, D.; Lindsey, W.; Lollo, B.; Mayfield, W.; Mehan, M.; Mehler, R.; Nelson, S.K.; Nelson, M.; Nieuwlandt, D.; Nikrad, M.; Ochsner, U.; Ostroff, R.M.; Otis, M.; Parker, T.; Pietrasiewicz, S.; Resnicow, D.I.; Rohloff, J.; Sanders, G.; Sattin, S.; Schneider, D.; Singer, B.; Stanton, M.; Sterkel, A.; Stewart, A.; Stratford, S.; Vaught, J.D.; Vrkljan, M.; Walker, J.J.; Watrobka, M.; Waugh, S.; Weiss, A.; Wilcox, S.K.; Wolfson, A.; Wolk, S.K.; Zhang, C.; Zichi, D. Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS One, 2010, 5(12), e15004.
[] [PMID: 21165148]
Liu, H.; Ponniah, G.; Zhang, H.M.; Nowak, C.; Neill, A.; Gonzalez-Lopez, N.; Patel, R.; Cheng, G.; Kita, A.Z.; Andrien, B. In vitro and in vivo modifications of recombinant and human IgG antibodies. mAbs-Austin, 2014, 6(5), 1145-1154.
Kumar Kulabhusan, P.; Hussain, B.; Yüce, M. Current perspectives on Aptamers as diagnostic tools and therapeutic agents. Pharmaceutics, 2020, 12(7), 646.
[] [PMID: 32659966]
Goringer, H.; Adler, A.; Forster, N.; Homann, M. Post-SELEX chemical optimization of a trypanosome-specific RNA aptamer. Comb. Chem. High Throughput Screen., 2008, 11(1), 16-23.
[] [PMID: 18220540]
Vater, A.; Klussmann, S. Turning mirror-image oligonucleotides into drugs: The evolution of Spiegelmer® therapeutics. Drug Discov. Today, 2015, 20(1), 147-155.
[] [PMID: 25236655]
Amero, P.; Khatua, S.; Rodriguez-Aguayo, C.; Lopez-Berestein, G. Aptamers: Novel therapeutics and potential role in neuro-oncology. Cancers (Basel), 2020, 12(10), 2889.
[] [PMID: 33050158]
Wang, R.E.; Wu, H.; Niu, Y.; Cai, J. Improving the stability of aptamers by chemical modification. Curr. Med. Chem., 2011, 18(27), 4126-4138.
[] [PMID: 21838692]
Henry, S.P.; Giclas, P.C.; Leeds, J.; Pangburn, M.; Auletta, C.; Levin, A.A.; Kornbrust, D.J. Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: Potential mechanism of action. J. Pharmacol. Exp. Ther., 1997, 281(2), 810-816.
[PMID: 9152389]
Winkler, J. Therapeutic oligonucleotides with polyethylene glycol modifications. Future Med. Chem., 2015, 7(13), 1721-1731.
[] [PMID: 26465713]
Nimjee, S.M.; White, R.R.; Becker, R.C.; Sullenger, B.A. Aptamers as therapeutics. Annu. Rev. Pharmacol. Toxicol., 2017, 57(1), 61-79.
[] [PMID: 28061688]
Keefe, A.D.; Pai, S.; Ellington, A. Aptamers as therapeutics. Nat. Rev. Drug Discov., 2010, 9(7), 537-550.
[] [PMID: 20592747]
Jain, S.; Kaur, J.; Prasad, S.; Roy, I. Nucleic acid therapeutics: A focus on the development of aptamers. Expert Opin. Drug Discov., 2021, 16(3), 255-274.
[] [PMID: 32990095]
Lincoff, A.M.; Mehran, R.; Povsic, T.J.; Zelenkofske, S.L.; Huang, Z.; Armstrong, P.W.; Steg, P.G.; Bode, C.; Cohen, M.G.; Buller, C.; Laanmets, P.; Valgimigli, M.; Marandi, T.; Fridrich, V.; Cantor, W.J.; Merkely, B.; Lopez-Sendon, J.; Cornel, J.H.; Kasprzak, J.D.; Aschermann, M.; Guetta, V.; Morais, J.; Sinnaeve, P.R.; Huber, K.; Stables, R.; Sellers, M.A.; Borgman, M.; Glenn, L.; Levinson, A.I.; Lopes, R.D.; Hasselblad, V.; Becker, R.C.; Alexander, J.H. Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): A randomised clinical trial. Lancet, 2016, 387(10016), 349-356.
[] [PMID: 26547100]
Sundaram, P.; Kurniawan, H.; Byrne, M.E.; Wower, J. Therapeutic RNA aptamers in clinical trials. Eur. J. Pharm. Sci., 2013, 48(1-2), 259-271.
[] [PMID: 23142634]
Rettig, G.R.; Behlke, M.A. Progress toward in vivo use of siRNAs-II. Mol. Ther., 2012, 20(3), 483-512.
[] [PMID: 22186795]
Petersen, M.; Wengel, J. LNA: A versatile tool for therapeutics and genomics. Trends Biotechnol., 2003, 21(2), 74-81.
[] [PMID: 12573856]
Hamaguchi, N.; Ellington, A.; Stanton, M. Aptamer beacons for the direct detection of proteins. Anal. Biochem., 2001, 294(2), 126-131.
[] [PMID: 11444807]
Schmidt, K.S.; Borkowski, S.; Kurreck, J.; Stephens, A.W.; Bald, R.; Hecht, M.; Friebe, M.; Dinkelborg, L.; Erdmann, V.A. Application of locked nucleic acids to improve aptamer in vivo stability and targeting function. Nucleic Acids Res., 2004, 32(19), 5757-5765.
[] [PMID: 15509871]
Shigdar, S.; Macdonald, J.; O’Connor, M.; Wang, T.; Xiang, D.; Al Shamaileh, H.; Qiao, L.; Wei, M.; Zhou, S.F.; Zhu, Y.; Kong, L.; Bhattacharya, S.; Li, C.; Duan, W. Aptamers as theranostic agents: Modifications, serum stability and functionalisation. Sensors (Basel), 2013, 13(10), 13624-13637.
[] [PMID: 24152925]
Burdick, A.D.; Sciabola, S.; Mantena, S.R.; Hollingshead, B.D.; Stanton, R.; Warneke, J.A.; Zeng, M.; Martsen, E.; Medvedev, A.; Makarov, S.S.; Reed, L.A.; Davis, J.W., II; Whiteley, L.O. Sequence motifs associated with hepatotoxicity of locked nucleic acid—modified antisense oligonucleotides. Nucleic Acids Res., 2014, 42(8), 4882-4891.
[] [PMID: 24550163]
Swayze, E.E.; Siwkowski, A.M.; Wancewicz, E.V.; Migawa, M.T.; Wyrzykiewicz, T.K.; Hung, G.; Monia, B.P.; Bennett, C.F. Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals. Nucleic Acids Res., 2007, 35(2), 687-700.
[] [PMID: 17182632]
Elskens, J.P.; Elskens, J.M.; Madder, A. Chemical modification of aptamers for increased binding affinity in diagnostic applications: Current status and future prospects. Int. J. Mol. Sci., 2020, 21(12), 4522.
[] [PMID: 32630547]
Maier, K.E.; Levy, M. From selection hits to clinical leads: Progress in aptamer discovery. Mol. Ther. Methods Clin. Dev., 2016, 3, 16014.
[] [PMID: 27088106]
Shen, W.; Liang, X.; Sun, H.; Crooke, S.T. 2′-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF. Nucleic Acids Res., 2015, 43(9), 4569-4578.
[] [PMID: 25855809]
Shen, W.; De Hoyos, C.L.; Sun, H.; Vickers, T.A.; Liang, X.; Crooke, S.T. Acute hepatotoxicity of 2′ fluoro-modified 5–10–5 gapmer phosphorothioate oligonucleotides in mice correlates with intracellular protein binding and the loss of DBHS proteins. Nucleic Acids Res., 2018, 46(5), 2204-2217.
[] [PMID: 29390093]
Pasternak, A.; Hernandez, F.J.; Rasmussen, L.M.; Vester, B.; Wengel, J. Improved thrombin binding aptamer by incorporation of a single unlocked nucleic acid monomer. Nucleic Acids Res., 2011, 39(3), 1155-1164.
[] [PMID: 20870750]
Li, X.; Li, Z.; Yu, H. Selection of threose nucleic acid aptamers to block PD-1/PD-L1 interaction for cancer immunotherapy. Chem. Commun. (Camb.), 2020, 56(93), 14653-14656.
[] [PMID: 33155587]
Skiba, J.; Kowalczyk, A.; Fik, M.A.; Gapińska, M.; Trzybiński, D.; Woźniak, K.; Vrček, V.; Czerwieniec, R.; Kowalski, K. Luminescent pyrenyl-GNA nucleosides: Synthesis, photophysics and confocal microscopy studies in cancer HeLa cells. Photochem. Photobiol. Sci., 2019, 18(10), 2449-2460.
[] [PMID: 31407765]
Tan, J.; Zhao, M.; Wang, J.; Li, Z.; Liang, L.; Zhang, L.; Yuan, Q.; Tan, W. Regulation of protein activity and cellular functions mediated by molecularly evolved nucleic acids. Angew. Chem. Int. Ed., 2019, 58(6), 1621-1625.
[] [PMID: 30556364]
Ni, S.; Zhuo, Z.; Pan, Y.; Yu, Y.; Li, F.; Liu, J.; Wang, L.; Wu, X.; Li, D.; Wan, Y.; Zhang, L.; Yang, Z.; Zhang, B.T.; Lu, A.; Zhang, G. Recent progress in aptamer discoveries and modifications for therapeutic applications. ACS Appl. Mater. Interfaces, 2021, 13(8), 9500-9519.
[] [PMID: 32603135]
Zhou, J.; Rossi, J.J. Cell-specific aptamer-mediated targeted drug delivery. Oligonucleotides, 2011, 21(1), 1-10.
[] [PMID: 21182455]
Meyer, C.; Eydeler, K.; Magbanua, E.; Zivkovic, T.; Piganeau, N.; Lorenzen, I.; Grötzinger, J.; Mayer, G.; Rose-John, S.; Hahn, U. Interleukin-6 receptor specific RNA aptamers for cargo delivery into target cells. RNA Biol., 2012, 9(1), 67-80.
[] [PMID: 22258147]
Zhu, G.; Niu, G.; Chen, X. Aptamer–drug conjugates. Bioconjug. Chem., 2015, 26(11), 2186-2197.
[] [PMID: 26083153]
Powell Gray, B.; Kelly, L.; Ahrens, D.P.; Barry, A.P.; Kratschmer, C.; Levy, M.; Sullenger, B.A. Tunable cytotoxic aptamer–drug conjugates for the treatment of prostate cancer. Proc. Natl. Acad. Sci. USA, 2018, 115(18), 4761-4766.
[] [PMID: 29666232]
Deng, Z.; Yang, Q.; Peng, Y.; He, J.; Xu, S.; Wang, D.; Peng, T.; Wang, R.; Wang, X.Q.; Tan, W. Polymeric engineering of aptamer–drug conjugates for targeted cancer therapy. Bioconjug. Chem., 2020, 31(1), 37-42.
[] [PMID: 31815437]
Fu, Z.; Xiang, J. Aptamer-functionalized nanoparticles in targeted delivery and cancer therapy. Int. J. Mol. Sci., 2020, 21(23), 9123.
[] [PMID: 33266216]
Chen, C.; Yang, Z.; Tang, X. Chemical modifications of nucleic acid drugs and their delivery systems for gene-based therapy. Med. Res. Rev., 2018, 38(3), 829-869.
[] [PMID: 29315675]
Vorobyeva, M.; Vorobjev, P.; Venyaminova, A. Multivalent Aptamers: Versatile tools for diagnostic and therapeutic applications. Molecules, 2016, 21(12), 1613.
[] [PMID: 27898020]
Ng, E.W.M.; Adamis, A.P. Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can. J. Ophthalmol., 2005, 40(3), 352-368.
[] [PMID: 15947805]
Chakravarthy, U.; Adamis, A.P.; Cunningham, E.T., Jr; Goldbaum, M.; Guyer, D.R.; Katz, B.; Patel, M. Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration. Ophthalmology, 2006, 113(9), 1508.e1-1508.e25.
[PMID: 16828500]
Sivaprasad, S.; Acharya, N.; Hykin, P. Pegaptanib sodium for neovascular age-related macular degeneration: Clinical experience in the UK. Clin. Ophthalmol., 2008, 2(2), 347-354.
[PMID: 19668726]
Jaffe, G.J.; Ciulla, T.A.; Ciardella, A.P.; Devin, F.; Dugel, P.U.; Eandi, C.M.; Masonson, H.; Monés, J.; Pearlman, J.A.; Quaranta-El Maftouhi, M.; Ricci, F.; Westby, K.; Patel, S.C. Dual antagonism of PDGF and VEGF in neovascular age-related macular degeneration. Ophthalmology, 2017, 124(2), 224-234.
[] [PMID: 28029445]
Jaffe, G.J.; Eliott, D.; Wells, J.A.; Prenner, J.L.; Papp, A.; Patel, S. A phase 1 study of intravitreous E10030 in combination with Ranibizumab in neovascular age-related macular degeneration. Ophthalmology, 2016, 123(1), 78-85.
[] [PMID: 26499921]
Cheng, Y.; Zhao, G.; Zhang, S.; Nigim, F.; Zhou, G.; Yu, Z.; Song, Y.; Chen, Y.; Li, Y. AS1411-induced growth inhibition of glioma cells by up-regulation of p53 and down-regulation of Bcl-2 and Akt1 via nucleolin. PLoS One, 2016, 11(12), e0167094.
[] [PMID: 27907160]
Reyes-Reyes, E.M.; Bates, P.J. Characterizing oligonucleotide uptake in cultured cells: A case study using AS1411 Aptamer. Methods Mol. Biol., 2019, 2036, 173-186.
[] [PMID: 31410797]
Bates, P.J.; Laber, D.A.; Miller, D.M.; Thomas, S.D.; Trent, J.O. Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol., 2009, 86(3), 151-164.
[] [PMID: 19454272]
Cogoi, S.; Ballico, M.; Bonora, G.M.; Xodo, L.E. Antiproliferative activity of a triplex-forming oligonucleotide recognizing a Ki-ras polypurine/polypyrimidine motif correlates with protein binding. Cancer Gene Ther., 2004, 11(7), 465-476.
[] [PMID: 15118760]
Teng, Y.; Girvan, A.C.; Casson, L.K.; Pierce, W.M., Jr; Qian, M.; Thomas, S.D.; Bates, P.J. AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin. Cancer Res., 2007, 67(21), 10491-10500.
[] [PMID: 17974993]
Deng, R.; Shen, N.; Yang, Y.; Yu, H.; Xu, S.; Yang, Y.W.; Liu, S.; Meguellati, K.; Yan, F. Targeting epigenetic pathway with gold nanoparticles for acute myeloid leukemia therapy. Biomaterials, 2018, 167, 80-90.
[] [PMID: 29554483]
Jaffe, G.J.; Westby, K.; Csaky, K.G.; Monés, J.; Pearlman, J.A.; Patel, S.S.; Joondeph, B.C.; Randolph, J.; Masonson, H.; Rezaei, K.A. C5 inhibitor Avacincaptad Pegol for geographic atrophy due to age-related macular degeneration. Ophthalmology, 2021, 128(4), 576-586.
[] [PMID: 32882310]
Goebl, N.; Berridge, B.; Wroblewski, V.J.; Brown-Augsburger, P.L. Development of a sensitive and specific in situ hybridization technique for the cellular localization of antisense oligodeoxynucleotide drugs in tissue sections. Toxicol. Pathol., 2007, 35(4), 541-548.
[] [PMID: 17562487]
Biesecker, G.; Dihel, L.; Enney, K.; Bendele, R.A. Derivation of RNA aptamer inhibitors of human complement C5. Immunopharmacology, 1999, 42(1-3), 219-230.
[] [PMID: 10408383]
Du, H.; Rosbash, M. The U1 snRNP protein U1C recognizes the 5′ splice site in the absence of base pairing. Nature, 2002, 419(6902), 86-90.
[] [PMID: 12214237]
Cohen, M.G.; Purdy, D.A.; Rossi, J.S.; Grinfeld, L.R.; Myles, S.K.; Aberle, L.H.; Greenbaum, A.B.; Fry, E.; Chan, M.Y.; Tonkens, R.M.; Zelenkofske, S.; Alexander, J.H.; Harrington, R.A.; Rusconi, C.P.; Becker, R.C. First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention. Circulation, 2010, 122(6), 614-622.
[] [PMID: 20660806]
Dyke, C.K.; Steinhubl, S.R.; Kleiman, N.S.; Cannon, R.O.; Aberle, L.G.; Lin, M.; Myles, S.K.; Melloni, C.; Harrington, R.A.; Alexander, J.H.; Becker, R.C.; Rusconi, C.P. 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, 2006, 114(23), 2490-2497.
[] [PMID: 17101847]
Povsic, T.J.; Wargin, W.A.; Alexander, J.H.; Krasnow, J.; Krolick, M.; Cohen, M.G.; Mehran, R.; Buller, C.E.; Bode, C.; Zelenkofske, S.L.; Rusconi, C.P.; Becker, R.C. Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy. Eur. Heart J., 2011, 32(19), 2412-2419.
[] [PMID: 21724623]
Chan, M.Y.; Cohen, M.G.; Dyke, C.K.; Myles, S.K.; Aberle, L.G.; Lin, M.; Walder, J.; Steinhubl, S.R.; Gilchrist, I.C.; Kleiman, N.S.; Vorchheimer, D.A.; Chronos, N.; Melloni, C.; Alexander, J.H.; Harrington, R.A.; Tonkens, R.M.; Becker, R.C.; Rusconi, C.P. Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. Circulation, 2008, 117(22), 2865-2874.
[] [PMID: 18506005]
Chan, M.Y.; Rusconi, C.P.; Alexander, J.H.; Tonkens, R.M.; Harrington, R.A.; Becker, R.C. A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor. J. Thromb. Haemost., 2008, 6(5), 789-796.
[] [PMID: 18284597]
Gilbert, J.C.; DeFeo-Fraulini, T.; Hutabarat, R.M.; Horvath, C.J.; Merlino, P.G.; Marsh, H.N.; Healy, J.M.; BouFakhreddine, S.; Holohan, T.V.; Schaub, R.G. First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Circulation, 2007, 116(23), 2678-2686.
[] [PMID: 18025536]
Spiel, A.O.; Mayr, F.B.; Ladani, N.; Wagner, P.G.; Schaub, R.G.; Gilbert, J.C.; Jilma, B. The aptamer ARC1779 is a potent and specific inhibitor of von willebrand factor mediated ex vivo platelet function in acute myocardial infarction. Platelets, 2009, 20(5), 334-340.
[] [PMID: 19637097]
Jilma, B.; Siller-Matula, J.; Gilbert, J.; Knöbl, P.; Jilma-Stohlawetz, P.; Gorczyca, M. Inhibition of von Willebrand factor by ARC1779 in patients with acute thrombotic thrombocytopenic purpura. Thromb. Haemost., 2011, 105(3), 545-552.
[] [PMID: 21174003]
Jilma-Stohlawetz, P.; Gilbert, J.; Gorczyca, M.; Knöbl, P.; Jilma, B. A dose ranging phase I/II trial of the von Willebrand factor inhibiting aptamer ARC1779 in patients with congenital thrombotic thrombo-cytopenic purpura. Thromb. Haemost., 2011, 106(9), 391-397.
[] [PMID: 21833442]
Cataland, S.R.; Peyvandi, F.; Mannucci, P.M.; Lämmle, B.; Kremer Hovinga, J.A.; Machin, S.J.; Scully, M.; Rock, G.; Gilbert, J.C.; Yang, S.; Wu, H.; Jilma, B.; Knoebl, P. Initial experience from a double-blind, placebo-controlled, clinical outcome study of ARC1779 in patients with thrombotic thrombocytopenic purpura. Am. J. Hematol., 2012, 87(4), 430-432.
[] [PMID: 22367751]
Jilma, B.; Paulinska, P.; Jilma-Stohlawetz, P.; Gilbert, J.C.; Hutabarat, R.; Knöbl, P. A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease. Thromb. Haemost., 2010, 104(3), 563-570.
[PMID: 20589313]
Povsic, T.J.; Cohen, M.G.; Mehran, R.; Buller, C.E.; Bode, C.; Cornel, J.H.; Kasprzak, J.D.; Montalescot, G.; Joseph, D.; Wargin, W.A.; Rusconi, C.P.; Zelenkofske, S.L.; Becker, R.C.; Alexander, J.H. A randomized, partially blinded, multicenter, activecontrolled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system in patients with acute coronary syndromes: Design and rationale of the RADAR Phase IIb trial. Am. Heart J., 2011, 161(2), 261-268.e2, 2.
[] [PMID: 21315207]
Yu, D.; Wang, D.; Zhu, F.G.; Bhagat, L.; Dai, M.; Kandimalla, E.R.; Agrawal, S. Modifications incorporated in CpG motifs of oligodeoxynucleotides lead to antagonist activity of toll-like receptors 7 and 9. J. Med. Chem., 2009, 52(16), 5108-5114.
[] [PMID: 19650625]
Cooper, C.L.; Ahluwalia, N.K.; Efler, S.M.; Vollmer, J.; Krieg, A.M.; Davis, H.L. Immunostimulatory effects of three classes of CpG oligodeoxynucleotides on PBMC from HCV chronic carriers. J. Immune Based Ther. Vaccines, 2008, 6(1), 3.
[] [PMID: 18541039]
Povsic, T.J.; Vavalle, J.P.; Aberle, L.H.; Kasprzak, J.D.; Cohen, M.G.; Mehran, R.; Bode, C.; Buller, C.E.; Montalescot, G.; Cornel, J.H.; Rynkiewicz, A.; Ring, M.E.; Zeymer, U.; Natarajan, M.; Delarche, N.; Zelenkofske, S.L.; Becker, R.C.; Alexander, J.H. A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: Results of the RADAR trial. Eur. Heart J., 2013, 34(31), 2481-2489.
[] [PMID: 22859796]
Becker, R.C.; Chan, M.Y. REG-1, a regimen comprising RB-006, a Factor IXa antagonist, and its oligonucleotide active control agent RB-007 for the potential treatment of arterial thrombosis. Curr. Opin. Mol. Ther., 2009, 11(6), 707-715.
[PMID: 20072947]
Kulkarni, O.; Eulberg, D.; Selve, N.; Zöllner, S.; Allam, R.; Pawar, R.D.; Pfeiffer, S.; Segerer, S.; Klussmann, S.; Anders, H.J. 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., 2009, 328(2), 371-377.
[] [PMID: 18997060]
Maasch, C.; Buchner, K.; Eulberg, D.; Vonhoff, S.; Klussmann, S. Physicochemical stability of NOX-E36, a 40mer L-RNA (Spiegelmer) for therapeutic applications. Nucleic Acids Symp. Ser., 2008, 52(1), 61-62.
[] [PMID: 18776253]
Zboralski, D.; Hoehlig, K.; Eulberg, D.; Frömming, A.; Vater, A. Increasing tumor-infiltrating T cells through inhibition of CXCL12 with NOX-A12 synergizes with PD-1 blockade. Cancer Immunol. Res., 2017, 5(11), 950-956.
[] [PMID: 28963140]
Steurer, M.; Montillo, M.; Scarfò, L.; Mauro, F.R.; Andel, J.; Wildner, S.; Trentin, L.; Janssens, A.; Burgstaller, S.; Frömming, A.; Dümmler, T.; Riecke, K.; Baumann, M.; Beyer, D.; Vauléon, S.; Ghia, P.; Foà, R.; Caligaris-Cappio, F.; Gobbi, M. Olaptesed pegol (NOX-A12) with bendamustine and rituximab: a phase IIa study in patients with relapsed/refractory chronic lymphocytic leukemia. Haematologica, 2019, 104(10), 2053-2060.
[] [PMID: 31097627]
Zavyalova, E.; Legatova, V.; Alieva, R.; Zalevsky, A.; Tashlitsky, V.; Arutyunyan, A.; Kopylov, A. Putative mechanisms underlying high inhibitory activities of bimodular DNA Aptamers to thrombin. Biomolecules, 2019, 9(2), 41.
[] [PMID: 30682825]
Sheehan, J.P.; Phan, T.M. Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex by an allosteric mechanism. Biochemistry, 2001, 40(16), 4980-4989.
[] [PMID: 11305914]
Schwoebel, F.; van Eijk, L.T.; Zboralski, D.; Sell, S.; Buchner, K.; Maasch, C.; Purschke, W.G.; Humphrey, M.; Zöllner, S.; Eulberg, D.; Morich, F.; Pickkers, P.; Klussmann, S. The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood, 2013, 121(12), 2311-2315.
[] [PMID: 23349391]
Boyce, M.; Warrington, S.; Cortezi, B.; Zöllner, S.; Vauléon, S.; Swinkels, D.W.; Summo, L.; Schwoebel, F.; Riecke, K. Safety, pharmacokinetics and pharmacodynamics of the anti‐hepcidin Spiegelmer lexaptepid pegol in healthy subjects. Br. J. Pharmacol., 2016, 173(10), 1580-1588.
[] [PMID: 26773325]
van Eijk, L.T.; John, A.S.E.; Schwoebel, F.; Summo, L.; Vauléon, S.; Zöllner, S.; Laarakkers, C.M.; Kox, M.; van der Hoeven, J.G.; Swinkels, D.W.; Riecke, K.; Pickkers, P. Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood, 2014, 124(17), 2643-2646.
[] [PMID: 25163699]
Eyetech Study Group. Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina, 2002, 22(2), 143-152.
[] [PMID: 11927845]
Ramirez-Carracedo, R.; Tesoro, L.; Hernandez, I.; Diez-Mata, J.; Piñeiro, D.; Hernandez-Jimenez, M.; Zamorano, J.L.; Zaragoza, C. Targeting TLR4 with ApTOLL improves heart function in response to coronary ischemia reperfusion in pigs undergoing acute myocardial infarction. Biomolecules, 2020, 10(8), 1167.
[] [PMID: 32784904]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy