Abstract
Many signalling proteins involved in diverse functions such as cell growth and differentiation can act as oncogenes and cause cellular transformation. These molecules represent attractive targets for cancer diagnosis or therapy and therefore are subject to intensive investigation.
Aptamers are small, highly structured nucleic acid molecules, isolated from combinatorial libraries by a procedure termed SELEX. Aptamers bind to a target molecule by providing a limited number of specific contact points imbedded in a larger, defined three-dimensional structure. Recently, aptamers have been selected against whole living cells, opening a new path which presents three major advantages: (1) direct selection without prior purification of membrane-bound targets, (2) access to membrane proteins in their native conformation similar to the in vivo conditions and (3) identification of (new) targets related to a specific phenotype. The ability to raise aptamers against living cells opens some attractive possibilities for new therapeutic and delivery approaches. In this chapter, the most recent advances in the field will be reviewed together with detailed descriptions of the relevant experimental approaches.
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References
Tuerk, C. and Gold, L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505–510.
Ellington, A.D. and Szostak, J.W. (1990) In vitro selection of RNA molecules that bind specific ligands. Science 346, 818–822.
Bock, L.C., Griffin, L.C., Latham, J.A., Vermaas, E.H. and Toole, J.J. (1992) Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355, 564–566.
Osborne, S.E. and Ellington, A.D. (1997) Nucleic acid selection and the challenge of combinatorial chemistry. Chem. Rev. 97, 349–370.
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.
Famulok, M. and Mayer, G. (2005). Intramers and aptamers: applications in protein-function analyses and potential for drug screening. ChemBioChem. 6, 19–26.
Morris, K.N., Jensen, K.B, Julin, C.M., Weil, M., Gold, L. (1998) High affinity ligands from in vitro selection: complex targets. Proc. Natl. Acad. Sci. U.S.A. 95, 2902–2907.
Homann, M. and Goringer, H.U. (1999) Combinatorial selection of high affinity RNA ligands to live African trypanosomes. Nucleic Acids Res. 27, 2006–2014.
Cerchia, L., Ducongé, F., Pestourie, C., Boulay, J., Aissouni, Y., Gombert, K., Tavitian, B, de Franciscis, V. and Libri, D. (2005) Neutralizing aptamers from whole-cell SELEX inhibit the RET receptor tyrosine kinase. PLoS Biol. 3, e123.
Gschwind, A., Fischer, O.M. and Ullrich, A. (2004). The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat. Rev. Cancer. 4, 361–370.
Pestourie, C., Cerchia, L., Gombert, K., Aissouni, Y., Boulay, J., de Franciscis, V., Libri, D., Tavitian, B. and Duconge, F. (2006) Comparison of different strategies to select aptamers against a transmembrane protein target. Oligonucleotides 16, 323–335.
Jhiang, S.M. (2000) The RET proto-oncogene in human cancers. Oncogene 19, 5590–5597.
Ichihara, M., Murakumo, Y. and Takahashi, M. (2004). RET and neuroendocrine tumors. Cancer Lett. 204,197–211.
Hansford, J.R. and Mulligan, L.M. (2000) Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis. J. Med. Genet. 37, 817–827.
Takahashi, M. (2001) The GDNF/Ret signaling pathway and human diseases. Cytokine Growth Factor Rev. 12, 361–373.
Putzer, B.M. and Drosten, M. (2004) The RET proto-oncogene: a potential target for molecular cancer therapy. Trends Mol. Med. 10, 351–357.
Maniè, S., Santoro, M., Fusco, A. and Billaud, M. (2001) The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet. 17, 580–589.
Pirollo, K.F., Zon, G., Rait, A., Zhou, Q., Yu, W., Hogrefe, R. and Chang, E.H. (2006) Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery. Human Gene Ther. 17, 117–124.
Song, E., Zhu, P., Lee, S., Chowdhury, D., Kussman, S., Dykxhoorn, D.M., Feng, Y., Palliser, D., Weiner, D.B., Shankar, P., Marasco, W.A. and Lieberman, J. (2005) Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors.Nat. Biotechnol. 23, 709–717.
Sioud, M. (2006) Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: A central role for 2'-hydroxyl uridines in immune responses. Eur. J. Immunol. 36, 1222–1230.
Farokhzad, O.C., Cheng, J., Teply, B.A., Sherifi, I., Jon, S., Kantoff, P.W., Richie, J.P. and Langer, R. (2006) Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc. Natl. Acad. Sci. U.S.A. 103, 6315–6320.
Chu, T.C., Twu, K.T., Ellington, A.D. and Levy, M. (2006) Aptamer mediated siRNA delivery. Nucleic Acids Res. 34, e73.
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, 1005–1115.
Chen, C.H., Chernis, G.A., Hoang, V.Q. and Landgraf, R. (2003). 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. U.S.A. 100, 9226–9231.
Lupold, S.E., Hicke, B.J., Lin, Y. and Coffey, D.S. (2002). Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res. 62, 4029–4033.
Mi, J., Zhang, X., Giangrande, P.H., McNamara, J.O., 2nd, Nimjee, S.M., Sarraf-Yazdi, S., Sullenger, B.A. and Clary, B.M. (2005). Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival. Biochem. Biophys. Res. Commun. 338, 956–963.
Mori, T., Oguro, A., Ohtsu, T. and Nakamura, Y (2004). RNA aptamers selected against the receptor activator of NF-kappaB acquire general affinity to proteins of the tumor necrosis factor receptor family. Nucleic Acids Res. 32, 6120–6128.
Acknowledgements
This work was supported by the European Molecular Imaging Laboratory (EMIL) Network (LSHC-2004-503569) and by the MIUR-FIRB Grant (#RBIN04J4J7).
We wish to thank C.L. Esposito, B. Tavitian, F. Duconge and D. Libri for fruitful discussions.
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Cerchia, L., Giangrande, P.H., McNamara, J.O., de Franciscis, V. (2009). Cell-Specific Aptamers for Targeted Therapies. In: Mayer, G. (eds) Nucleic Acid and Peptide Aptamers. Methods in Molecular Biology™, vol 535. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-557-2_5
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DOI: https://doi.org/10.1007/978-1-59745-557-2_5
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