Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Cellular and Molecular Biology Letters

Editor-in-Chief: /

IMPACT FACTOR 2016: 1.260
5-year IMPACT FACTOR: 1.506

CiteScore 2016: 1.56

SCImago Journal Rank (SJR) 2016: 0.615
Source Normalized Impact per Paper (SNIP) 2016: 0.470

See all formats and pricing
More options …
Volume 16, Issue 1 (Mar 2011)

The selection of aptamers specific for membrane molecular targets

Teresa Janas / Tadeusz Janas
Published Online: 2011-01-13 | DOI: https://doi.org/10.2478/s11658-010-0023-3


A growing number of RNA aptamers have been selected experimentally using the SELEX combinatorial approach, and these aptamers have several advantages over monoclonal protein antibodies or peptides with respect to their applications in medicine and nanobiotechnology. Relatively few successful selections have been reported for membrane molecular targets, in contrast to the situation with non-membrane molecular targets. This review compares the procedures and techniques used in selections against membrane proteins and membrane lipids. In the case of membrane proteins, the selections were performed against soluble protein fragments, detergent-membrane protein mixed micelles, whole cells, vesicles derived from cellular membranes, and enveloped viruses. Liposomes were used as an experimental system for the selection of aptamers against membrane lipids. RNA structure-dependent aptamer binding for rafts in lipid vesicles was reported. Based on the selected aptamers against DOPC and the amino acid tryptophan, a specific passive membrane transporter composed of RNA was constructed. The determination of the selectivity of aptamers appears to be a crucial step in a selection, but has rarely been fully investigated. The selections, which use whole cells or vesicles derived from membranes, can yield aptamers not only against proteins but also against membrane lipids.

Keywords: RNA; SELEX; Aptamers; Membranes; Membrane proteins; Lipids; Liposomes; Rafts; Membrane transporters

  • [1] Yarus, M. Life from an RNA World: the ancestor within. Harvard University Press, New York, 2010. Google Scholar

  • [2] Connell, G.J., Illangsekare, M., Yarus, M. Three small ribooligonucleotides with specific arginine sites. Biochemistry 32 (1993) 5497–5502. http://dx.doi.org/10.1021/bi00072a002CrossrefGoogle Scholar

  • [3] Khvorova, A., Kwak, Y.-G., Tamkun, M., Majerfeld, I. and Yarus, M. RNAs that bind and change the permeability of phospholipid membranes. Proc. Natl. Acad. Sci. USA 96 (1999) 10649–10654. http://dx.doi.org/10.1073/pnas.96.19.10649CrossrefGoogle Scholar

  • [4] Yarus, M. A specific amino acid binding site composed of RNA. Science 240 (1988) 1751–1758. http://dx.doi.org/10.1126/science.3381099CrossrefGoogle Scholar

  • [5] Roth, A., Winkler, W.C., Regulski, E.E., Lee, B.W.K., Lim, J., Jona, I., Barrick, J.E., Ritwik, A., Kim, J.N., Welz, R., Iwata-Reuyl, D. and Breaker, R.R. A riboswitch selective for the queuosine precursor preQ1 contains an unusually small aptamer domain. Nat. Struct. Mol. Biol. 14 (2007) 308–317. http://dx.doi.org/10.1038/nsmb1224CrossrefGoogle Scholar

  • [6] Spitale, R.C., Terelli, A.T., Krucinska, J., Bandarlan, V., Wedekind, J.E. The structural basis for recognition of the preQ0 metabolite by an unusually small riboswitch aptamer domain. J. Biol. Chem. 284 (2009) 11012–11016. http://dx.doi.org/10.1074/jbc.C900024200CrossrefGoogle Scholar

  • [7] Ellington, A.D. and Szostak, J. W. In vitro selection of RNA molecules that bind specific ligands. Nature 346 (1990) 818–822. http://dx.doi.org/10.1038/346818a0CrossrefGoogle Scholar

  • [8] Tuerk, C. and Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA-polymerase. Science 249 (1990) 505–510. http://dx.doi.org/10.1126/science.2200121CrossrefGoogle Scholar

  • [9] Janas, T., Widmann, J.J., Knight, R. and Yarus, M. Simple, recurrent RNA binding sites for L-arginine. RNA (2010) 805–816. CrossrefGoogle Scholar

  • [10] Bock, L.C., Griffin, L.C., Latham, J.A., Vermaas, E.H. and Toole, J.J. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355 (1992) 564–566. http://dx.doi.org/10.1038/355564a0CrossrefGoogle Scholar

  • [11] Anderson, P.C. and Mecozzi, S. Unusually short RNA sequences: design of a 13-mer RNA that selectively binds and recognizes theophylline. J. Am. Chem. Soc. 127 (2005) 5290–5291. http://dx.doi.org/10.1021/ja0432463CrossrefGoogle Scholar

  • [12] Farokhzad, O.C., Cheng, J., Teply, B.A., Sherifi, I., Jon, S., Kantoff, P.W., Richie, J.P. and Langer, R. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc. Natl. Acad. Sci. USA 103 (2006) 6315–6320. http://dx.doi.org/10.1073/pnas.0601755103CrossrefGoogle Scholar

  • [13] Song, S., Wang, L., Li, J., Zhao, J. and Fan, C. Aptamer-based biosensors. Trends Anal. Chem. 27 (2008) 108–117. http://dx.doi.org/10.1016/j.trac.2007.12.004CrossrefGoogle Scholar

  • [14] Lee, J.O., So, H.M., Jeon, E.K., Chang, H., Won, K. and Kim, Y.H. Aptamers as molecular recognition elements for electrical nanobiosensors. Anal. Bioanal. Chem. 390 (2008) 1023–1032. http://dx.doi.org/10.1007/s00216-007-1643-yCrossrefGoogle Scholar

  • [15] Barbas, A.S. and White, R.R. The development and testing for cancer. Curr. Opin. Investig. Drugs 10 (2009) 572–578. Google Scholar

  • [16] Hicke, B.J., Marion, C., Chang, Y.F., Gould, T., Lynott, C.K., Parma, D., Schmidt, P.G. and Warren, S. Tenascin-C aptamers are generated using tumor cells and purified protein. J. Biol. Chem. 276 (2001) 48644–48654. http://dx.doi.org/10.1074/jbc.M104651200CrossrefGoogle Scholar

  • [17] Pestourie, C. Tavitian, B. and Duconge, F. Aptamets against extracellular targets for in vivo applications. Biochimie 87 (2005) 921–930. http://dx.doi.org/10.1016/j.biochi.2005.04.013CrossrefGoogle Scholar

  • [18] Janas, T., Janas, T. and Yarus, M. RNA, lipids and membranes. in: The RNA World III (Gesteland,, R., Cech, T.R. and Atkins, J., Eds.), Cold Spring Harbor Laboratory Press, 2006, 207–225. Google Scholar

  • [19] Shamah, S.M., Healy, J.M. and Cload, S.T. Complex target SELEX. Acc. Chem. Res. 41 (2008) 130–138. http://dx.doi.org/10.1021/ar700142zCrossrefGoogle Scholar

  • [20] Li, N., Ebright, J.N., Stovall, G.M., Chen, X., Nguyen, H.H., Singh, A., Syrett, A. and Ellington, A.D. Technical and biological issues relevant to cell typing with aptamers. J. Proteome Res. 8 (2009) 2438–2448. http://dx.doi.org/10.1021/pr801048zCrossrefGoogle Scholar

  • [21] Lupold, S.E., Hicke, B.J., Lin, Y. and 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. 62 (2002) 4029–4033. Google Scholar

  • [22] Chen, C.h.B., Chernis, G.A., Hoang, V.Q. and Landgraf, R. Inhibition of heregulin signaling by an aptamer that preferentially binds to the oligomeric form of human epidermal growth factor receptor-3. Proc. Natl. Acad. Sci. USA 100 (2003) 9226–9231. http://dx.doi.org/10.1073/pnas.1332660100CrossrefGoogle Scholar

  • [23] Rentmeister, A., Bill, A., Wahle, T., Walter, J. and Famulok, M. RNA aptamers selectively modulate protein recruitment to the cytoplasmic domain of β-secretase BACE1 in vitro. RNA 12 (2006) 1650–1660. http://dx.doi.org/10.1261/rna.126306Google Scholar

  • [24] O’Connell, D., Koenig, A., Jennings, S., Hicke, B., Han, H.L., Fitzwater, T., Chang, Y.F., Varki, N., Parma, D. and Varki, A. Calcium-dependent oligonucleotide antagonists specific for L-selectin. Proc. Natl. Acad. Sci. USA 93 (1996) 5883–5887. http://dx.doi.org/10.1073/pnas.93.12.5883CrossrefGoogle Scholar

  • [25] Lee, H.K., Choi, Y.S., Park, Y.A. and Jeong, S. Modulation of oncogenic transcription and alternative splicing by β-catenin and an RNA aptamer in colon cancer cells. Cancer Res. 66 (2006) 10560–10566. http://dx.doi.org/10.1158/0008-5472.CAN-06-2526CrossrefGoogle Scholar

  • [26] Tanaka, Y., Akagi, K., Nakamura, Y. and Kozu, T. RNA aptamers targeting the carboxyl terminus of KRAS oncoprotein generated by an improved SELEX with isothermal RNA amplification. Oligonucleotides 17 (2007) 12–21. http://dx.doi.org/10.1089/oli.2006.0035R1CrossrefGoogle Scholar

  • [27] Jeon, S.H., Kayhan, B., Ben-Yedidia, T. and Arnon, R. A DNA aptamer prevents influenza infection by blocking the receptor binding region of the viral hemagglutinin. J. Biol. Chem. 279 (2004) 48410–48419. http://dx.doi.org/10.1074/jbc.M409059200CrossrefGoogle Scholar

  • [28] Ferreira, C.S.M., Matthews, C.S. and Missailidis, S. DNA aptamers that bind to MUC1 tumour marker: design and characterization of MUC1-binding single-stranded DNA aptamers. Tumor Biol. 27 (2006) 289–301. http://dx.doi.org/10.1159/000096085Google Scholar

  • [29] Daniels, D.A., Sohal, A.K., Rees, S. and Grisshammer, R. Generation of RNA aptamers to the G-protein-coupled receptor for neurotensin, NTS-1. Anal. Biochem. 305 (2002) 214–226. http://dx.doi.org/10.1006/abio.2002.5663Google Scholar

  • [30] Joshi, R., Janagama, H., Dwivedi, H.P., Kumar, T.M.A.S., Jaykus, L.A. Schefers, J. and Sreevatsan, S. Selection, characterization, and application of DNA aptamers for the capture and detection of Salmonella enterica serovars. Mol. Cell. Probes 23 (2009) 20–28. http://dx.doi.org/10.1016/j.mcp.2008.10.006CrossrefGoogle Scholar

  • [31] Ulrich, H., Ippolito, J.E., Pagan, O.R., Eterovic, V.A., Hann, R.M., Shi, H., Lis, J.T., Eldefrawi, M.E. and Hess, G.P. In vitro selection of RNA molecules that displace cocaine from the membrane-bound nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. USA 95 (1998) 14051–14056. http://dx.doi.org/10.1073/pnas.95.24.14051CrossrefGoogle Scholar

  • [32] Morris, K.N., Jensen, K.B., Julin, C.M., Weil, M. and Gold, L. High affinity ligands from in vitro selection: complex target. Proc. Natl. Acad. Sci. USA 95 (1998) 2902–2907. http://dx.doi.org/10.1073/pnas.95.6.2902CrossrefGoogle Scholar

  • [33] Shangguan, D., Li, Y., Tang, Z., Cao, Z.C., Chen, H.W., Mallikaratchy, P., Sefah, K., Yang, C.J. and Tan, W. Aptamers evolved from live cells as effective molecular probes for cancer study. Proc. Natl. Acad. Sci. USA 103 (2006) 11838–11843. http://dx.doi.org/10.1073/pnas.0602615103CrossrefGoogle Scholar

  • [34] Homann, M. and Göringer, H.U. Combinatorial selection of high affinity RNA ligands to live African trypanosomes. Nucleic Acids Res. 27 (1999) 2006–2014. http://dx.doi.org/10.1093/nar/27.9.2006CrossrefGoogle Scholar

  • [35] Blank, M., Weinschenk, T., Priemer, M. and Schluesener, H. Systematic evolution of DNA aptamer binding to rat brain tumor microvessels. J. Biol. Chem. 276 (2001) 16464–16468. http://dx.doi.org/10.1074/jbc.M100347200CrossrefGoogle Scholar

  • [36] Mallikaratchy, P., Tang, Z., Kwame, S., Meng, L., Shangguan, D. and Tan, W. Aptamer directly evolved from live cells recognizes membrane bound immunoglobin heavy mu chain in Burkitt’s lymphoma cells. Mol. Cell. Proteomics 6 (2007) 2230–2238. http://dx.doi.org/10.1074/mcp.M700026-MCP200CrossrefGoogle Scholar

  • [37] Shangguan, D., Cao, Z., Meng, L., Mallikaratchy, P., Sefah, K., Wang, H., Li, Y. and Tan, W. Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J. Proteome Res. 7 (2008) 2133–2139. http://dx.doi.org/10.1021/pr700894dCrossrefGoogle Scholar

  • [38] Berezovski, M.V., Lechmann, M., Musheev, M.U., Mak, T.W. and Krylov, S.N. Aptamer-facilitated biomarker discovery (AptaBiD). J. Am. Chem. Soc. 130 (2008) 9137–9143. http://dx.doi.org/10.1021/ja801951pCrossrefGoogle Scholar

  • [39] Ulrich, H., Magdesian, M.H., Alves, M.J.M. and Colli, W. In vitro selection of RNA aptamers that bind to cell adhesion receptors of Trypanosoma cruzi and inhibit cell invasion. J. Biol. Chem. 277 (2002) 20756–20762. http://dx.doi.org/10.1074/jbc.M111859200CrossrefGoogle Scholar

  • [40] Cerchia, L., Duconge, F., Pestourie, C., Boulay, J., Aissouni, Y., Gombert, K., Tavitian, B., de Franciscis, V. and Libri, D. Neutralizing aptamers from whole-cell SELEX inhibit the RET receptor tyrosine kinase. PLOS Biol. 3 (2005) 697–704. http://dx.doi.org/10.1371/journal.pbio.0030123CrossrefGoogle Scholar

  • [41] Gopinath, S.C.B., Misono, T.S., Kawasaki, K., Mizuno, T., Imai, M., Odegiri, T. and Kumar, P.K.R. An RNA aptamer that distinguishes between closely related human influenza viruses and inhibits haemagglutinin-mediated membrane fusion. J. Gen. Virol. 87 (2006) 479–487. http://dx.doi.org/10.1099/vir.0.81508-0CrossrefGoogle Scholar

  • [42] Ohuchi, S.P., Ohtsu, T. and Nakamura, Y. Selection of RNA aptamers against recombinant transforming growth factor-β type III receptor displayed on cell surface. Biochimie 88 (2006) 897–904. http://dx.doi.org/10.1016/j.biochi.2006.02.004CrossrefGoogle Scholar

  • [43] Sazani, P.L., Larraide, R. and Szostak, J.W. A small aptamer with strong and specific recognition of the triphosphate of ATP. J. Am. Chem Soc. 126 (2004) 8370–8371. http://dx.doi.org/10.1021/ja049171kCrossrefGoogle Scholar

  • [44] Zimmerman, G.R, Jenison, R.D., Wick, C.L., Simorre, J.P. and Pardi, A. Interlocking structural motifs mediate molecular discrimination by a theophylline-binding RNA. Nat. Struct. Biol. 4 (1997) 644–649. http://dx.doi.org/10.1038/nsb0897-644CrossrefGoogle Scholar

  • [45] Majerfeld, I. and Yarus, M. An RNA pocker for an aliphatic hydrophobe. Nature Struct. Biol. 1 (1994) 287–292. http://dx.doi.org/10.1038/nsb0594-287CrossrefGoogle Scholar

  • [46] Majerfeld, I. and Yarus, M. Isoleucine:RNA sites with associated coding sequences. RNA 4 (1998) 471–478. Google Scholar

  • [47] Gilbert, B.A., Sha, M., Wathen, S.T. and Rando, R.R. RNA aptamers that specifically bind to a K Ras-derived farnesylated peptide. Bioorg. Med. Chem. 5 (1997) 1115–1122. http://dx.doi.org/10.1016/S0968-0896(97)00047-3CrossrefGoogle Scholar

  • [48] Sussman, D., Nix, J.C. and Wilson, C. The structural basis for molecular recognition by the vitamin B12 RNA aptamer. Nat. Struct. Biol. 7 (2000) 53–57. http://dx.doi.org/10.1038/71253CrossrefGoogle Scholar

  • [49] Illangasekare, M. and Yarus, M. Phenylalanine-binding RNAs and genetic code evolution. J. Mol. Evol. 54 (2002) 298–311. CrossrefGoogle Scholar

  • [50] Betat, H., Vogel, S., Struhalla, M., Förster, H.H., Famulok, M., Welzel, P. and Hahn, U. Aptamers that recognize the lipid moiety of the antibiotic moenomycin A. Biol. Chem. 384 (2003) 1497–1500. http://dx.doi.org/10.1515/BC.2003.165CrossrefGoogle Scholar

  • [51] Brockstedt, U., Uzarowska, A., Montpetit, A., Pfau, W. and Labuda, D. In vitro evolution of RNA aptamers recognizing carcinogenic aromatic amines. Biochem. Biophys. Res Commun. 313 (2004) 1004–1008. http://dx.doi.org/10.1016/j.bbrc.2003.12.030CrossrefGoogle Scholar

  • [52] Janas, T., Janas, T. and Yarus, M. Specific RNA binding to ordered phospholipid bilayers. Nucleic Acids Res. 34 (2006) 2128–2136. http://dx.doi.org/10.1093/nar/gkl220CrossrefGoogle Scholar

  • [53] Vlassov, A., Khvorova, A., and Yarus, M. Binding and disruption of phosholipid bilayers by supramolecular RNA complexes. Proc. Natl. Acad. Sci. USA 98 (2001) 7706–7711. http://dx.doi.org/10.1073/pnas.141041098CrossrefGoogle Scholar

  • [54] Janas, T. and Yarus, M. Visualization of membrane RNAs. RNA 9 (2003) 1353–1361. http://dx.doi.org/10.1261/rna.5129803CrossrefGoogle Scholar

  • [55] Janas, T., Janas, T. and Yarus, M. A membrane transporter for tryptophan composed of RNA. RNA 10 (2004) 1541–1549. http://dx.doi.org/10.1261/rna.7112704CrossrefGoogle Scholar

  • [56] Janas, T. and Janas, T. A Search for membrane RNAs that can inhibit formation of toxic amyloid aggregates. Sie Foundation Symposium, Aurora, 2006, 13. Google Scholar

About the article

Published Online: 2011-01-13

Published in Print: 2011-03-01

Citation Information: Cellular and Molecular Biology Letters, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-010-0023-3.

Export Citation

© 2011 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Justyna M. Meissner, Monika Toporkiewicz, Aleksander Czogalla, Lucyna Matusewicz, Kazimierz Kuliczkowski, and Aleksander F. Sikorski
Journal of Controlled Release, 2015, Volume 220, Page 515
Corné H. van den Kieboom, Samantha L. van der Beek, Tamás Mészáros, Róbert E. Gyurcsányi, Gerben Ferwerda, and Marien I. de Jonge
TrAC Trends in Analytical Chemistry, 2015, Volume 74, Page 58
Teresa Janas, Maja M. Janas, Karolina Sapoń, and Tadeusz Janas
FEBS Letters, 2015, Volume 589, Number 13, Page 1391
Ádám Kun, András Szilágyi, Balázs Könnyű, Gergely Boza, István Zachar, and Eörs Szathmáry
Annals of the New York Academy of Sciences, 2015, Volume 1341, Number 1, Page 75
Eugenio F. Fornasiero and Felipe Opazo
BioEssays, 2015, Volume 37, Number 4, Page 436
Krzysztof Nowotarski, Karolina Sapoń, Monika Kowalska, Tadeusz Janas, and Teresa Janas
Cellular and Molecular Biology Letters, 2013, Volume 18, Number 4
Kepa Ruiz-Mirazo, Carlos Briones, and Andrés de la Escosura
Chemical Reviews, 2014, Volume 114, Number 1, Page 285
Elżbieta Piątkowska, Jerzy Piątkowski, and Anna Przondo-Mordarska
Cellular and Molecular Biology Letters, 2012, Volume 17, Number 4
Elyse D. Bernard, Michael A. Beking, Karunanithi Rajamanickam, Eve C. Tsai, and Maria C. DeRosa
JBIC Journal of Biological Inorganic Chemistry, 2012, Volume 17, Number 8, Page 1159
Athulya Aravind, Saino Hanna Varghese, Srivani Veeranarayanan, Anila Mathew, Yutaka Nagaoka, Seiki Iwai, Takahiro Fukuda, Takashi Hasumura, Yasuhiko Yoshida, Toru Maekawa, and D. Sakthi Kumar
Cancer Nanotechnology, 2012, Volume 3, Number 1-6, Page 1
Teresa Janas, Krzysztof Nowotarski, and Tadeusz Janas
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2011, Volume 1808, Number 9, Page 2322

Comments (0)

Please log in or register to comment.
Log in