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EMBO reports 6, 12, 1176–1181 (2005)
doi:10.1038/sj.embor.7400535
Published online: 16 September 2005
Phosphorothioate-stimulated uptake of short interfering RNA by human cells
Marita Overhoff & Georg Sczakiel
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Institut für Molekulare Medizin, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
To whom correspondence should be addressed
Georg Sczakiel Tel: +49 451 500 2730; Fax: +49 451 500 2729; E-mail: sczakiel@imm.uni-luebeck.de
Received 1 April 2005; Accepted 18 August 2005; Published online 16 September 2005.
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Abstract
The cellular delivery of short interfering RNA (siRNA) is a main hurdle in therapeutic drug development. Here, we describe that phosphorothioate (PTO)-derived oligonucleotides stimulate the physical cellular uptake of siRNA in trans in human cells. This is reflected by an apparent dose-dependent siRNA-mediated suppression of lamin A/C in primary human umbilical vein endothelial cells. The PTO-stimulated cellular uptake in trans is concentration dependent, length dependent, related to the phosphorothioate chemistry but not sequence specific. We provide experimental evidence to support a caveolin-mediated uptake mechanism. In sum, this work strongly suggests the exploration of PTOs as facilitators in the delivery of biologically active siRNA to mammalian cells.
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