Biodistribution of phosphodiester and phosphorothioate siRNA

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1139-43. doi: 10.1016/j.bmcl.2003.12.074.


Short interfering RNAs (siRNAs) are valuable tools for analyzing protein function in mammalian cell culture. This success has led to high expectations for in vivo and therapeutic applications. However, the pharmacokinetic properties of siRNA are not known. Here we report the biodistribution of a phosphodiester (PO) siRNA duplex and examine the effect of phosphorothioate (PS) linkages. Our findings indicate that biodistribution of siRNA is similar to that for single-stranded antisense oligonucleotides and offer insights for use of siRNA in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Availability
  • Brain / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Mice
  • Oligonucleotides / genetics
  • Oligonucleotides / pharmacokinetics
  • Organ Specificity
  • Organophosphates / pharmacokinetics
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacokinetics*
  • Tissue Distribution


  • Oligonucleotides
  • Organophosphates
  • RNA, Small Interfering