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Sci. Pharm. 2009, 77(Short Lectures (SL)), 171; doi:10.3797/scipharm.oephg.21.SL-04 (registering DOI)

Targeted Delivery of siRNA to Tumor Cells with Designed Ankyrin Repeat Protein Nanocomplexes

1
Department of Medicinal Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
2
Department of Pharmacology, University of Bern, Friedbühlstraße 49, 3010 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Received: 16 April 2009 / Accepted: 16 April 2009 / Published: 16 April 2009
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Abstract

Specific delivery to tumors and efficient cellular uptake of nucleic acids are major challenges for gene-targeted cancer therapies. Tumor-targeted delivery using antibody fragments or immunoliposomes have already been demonstrated to enhance cellular uptake of nucleic acids by receptor-mediated endocytosis. Here we report the first use of an epithelial cell adhesion molecule (EpCAM)-specific designed ankyrin repeat protein (DARPin) as a carrier for siRNA. Designed ankyrin repeat proteins are a novel class of non-immunoglobulin binding proteins relying on the modularity of ankyrins. Their short length, high stability, and the lack of intramolecular cysteines facilitate proper folding, result in high-yield expression in E. coli, and allow engineering procedures usually not well tolerated by antibodies. A DARPin binding to EpCAM was derived from a designed protein library using ribosome display.
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

WINKLER, J.; ZANGEMEISTER-WITTKE, U. Targeted Delivery of siRNA to Tumor Cells with Designed Ankyrin Repeat Protein Nanocomplexes. Sci. Pharm. 2009, 77, 171.

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