Efficient delivery of siRNA using dendritic poly(L-lysine) for loss-of-function analysis

J Control Release. 2008 Feb 18;126(1):59-66. doi: 10.1016/j.jconrel.2007.10.022. Epub 2007 Nov 6.

Abstract

RNA interference (RNAi) is a valuable tool for the validation of gene identification and functional genomics. Previously, it was reported that 6th generation dendritic poly(L-lysine) (KG6) transfected DNA into several cultivated cell lines with high efficiency and without any cytotoxic effects. In this study, the potential of KG6 to be an efficient siRNA carrier is investigated. KG6 showed effective knockdown of GAPDH with low cytotoxicity in combination with the weak-base amphiphilic peptide, Endo-Porter. In addition, the knockdown of PEPCK, which is the rate-limiting enzyme for gluconeogenesis, led to a reduction in glucose production in rat hepatoma H4IIEC3 cells. Knockdown of organic cation transporter 1 (OCT1), which is thought to be the gene that influences metformin action, was shown to successfully diminish the ability of metformin to inhibit gluconeogenesis in H4IIEC3 cells. In conclusion, using a combination of KG6 and Endo-Porter, a model system in which genes that influence metformin action can be identified was successfully constructed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catecholamine Plasma Membrane Transport Proteins / genetics
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dendrimers / chemistry*
  • Drug Carriers / chemistry*
  • Gluconeogenesis / drug effects
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / genetics
  • Metformin / pharmacology
  • Polylysine / chemistry*
  • Protein-Serine-Threonine Kinases / genetics
  • RNA Interference*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Rats
  • Transfection

Substances

  • Catecholamine Plasma Membrane Transport Proteins
  • Dendrimers
  • Drug Carriers
  • RNA, Small Interfering
  • Slc22a1 protein, rat
  • Polylysine
  • Metformin
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)
  • phosphoenolpyruvate carboxylase kinase
  • Protein-Serine-Threonine Kinases