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Nucleic acid aptamers for targeting of shRNA-based cancer therapeutics

Authors John S Vorhies, John J Nemunaitis

Published 15 February 2008 Volume 2007:1(4) Pages 367—376

John S Vorhies, John J Nemunaitis

Mary Crowley Cancer Research Centers, Dallas, TX, USA

Abstract: Aptamers are nucleic acid ligands which have been validated to bind to epitopes with a specificity similar to that of monoclonal antibodies. Aptamers have been primarily investigated for their direct function in terms of inhibition of protein targets; however, recent evidence gives reason to actively explore aptamers as targeting moieties for delivery of anticancer therapeutics. Many aptamers have been developed to bind to extracellular membrane domains of proteins over-expressed on cancer cells and have the potential to be modified for use in targeting cancer therapeutics. The use of DNA vector-based short hairpin RNA (shRNA) for RNA interference (RNAi) is a precise means for the disruption of target gene expression but its clinical usage in cancer is limited by obstacles related to delivery into cancer cells. Nucleic acid aptamers are attractive candidates for targeting of shRNA therapies. Their small size, ease of production and modification, and high specificity are valued attributes in comparison to other targeting moieties currently being tested. Here we review the development of aptamers directed to PSMA, Nucleolin, HER-3, RET, TN-C, and MUC1 and focus on their potential for use in targeting of shRNA-based cancer therapeutics.

Keywords: aptamer, tumor targeting, oligonucleotides therapeutics, cancer, shRNA, gene therapy

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