Phosphorothioate-stimulated uptake of short interfering RNA by human cells

Marita Overhoff, Georg Sczakiel*

*Corresponding author for this work
45 Citations (Scopus)


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.

Original languageEnglish
JournalEMBO Reports
Issue number12
Pages (from-to)1176-1181
Number of pages6
Publication statusPublished - 01.12.2005


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