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Phosphorothioate-stimulated uptake of short interfering RNA by human cells

Authors
  • Marita Overhoff
  • Georg Sczakiel
Publication Date
Sep 16, 2005
Source
PMC
Keywords
Disciplines
  • Biology
  • Chemistry
  • Medicine
License
Unknown

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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