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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Cell-specific induction of apoptosis by rationally designed bivalent aptamer-siRNA transcripts silencing eukaryotic elongation factor 2
Current Cancer Drug Targets, Volume 8, No. 7, Year 2008
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Description
New strategies for cell type-specific delivery need to be developed if RNA interference is to realize its full therapeutic potential. One possible approach is the use of aptamers to deliver siRNAs selectively to tumor cells with appropriate antigens displayed on the surface. We used an aptamer that binds specifically to PSMA, a cell surface glycoprotein found in abundance on prostate cancer cells, and joined its 3' end to a siRNA specific for Eukaryotic Elongation Factor 2 mRNA (EEF2). This is an attractive target for cancer therapy because inhibiting EEF2 causes the rapid arrest of protein synthesis, inducing apoptosis and leading ultimately to cell death. In order to enhance the therapeutic efficacy of the aptamer-siRNA, we increased the valency of the construct by rational design. Two anti-PSMA aptamers were designed such that each binding sequence could fold independently into its active conformation. Here we show specific cytotoxicity resulting from siRNA-induced silencing of EEF2, as well as specific delivery to PSMA-expressing prostate cancer cells. Increasing the valency of the aptamer resulted in enhanced cytotoxicity compared with the monovalent constructs. The results presented here demonstrate the usefulness of multivalent aptamer-based delivery vehicles for siRNA therapeutics. © 2008 Bentham Science Publishers Ltd.
Authors & Co-Authors
Kleines, Michael
Germany, Aachen
Uniklinik Rwth Aachen
Tur, Mehmet Kemal
Germany, Aachen
Rheinisch-westfälische Technische Hochschule Aachen
Barth, Stefan W.
Germany, Aachen
Fraunhofer Institute for Molecular Biology and Applied Ecology Ime
Germany, Aachen
Rheinisch-westfälische Technische Hochschule Aachen
Statistics
Citations: 104
Authors: 3
Affiliations: 4
Identifiers
Doi:
10.2174/156800908786241078
ISSN:
15680096
Research Areas
Cancer