Extracellular glycosaminoglycans modify cellular trafficking of lipoplexes and polyplexes

J Biol Chem. 2001 Sep 7;276(36):33875-80. doi: 10.1074/jbc.M011553200. Epub 2001 Jun 4.


It has been shown that extracellular glycosaminoglycans (GAGs) limit the gene transfer by cationic lipids and polymers. The purpose of this study was to clarify how interactions with anionic GAGs (hyaluronic acid and heparan sulfate) modify the cellular uptake and distribution of lipoplexes and polyplexes. Experiments on cellular DNA uptake and GFP reporter gene expression showed that decreased gene expression can rarely be explained by lower cellular uptake. In most cases, the cellular uptake is not changed by GAG binding to the lipoplexes or polyplexes. Reporter gene expression is decreased or blocked by heparan sulfate, but it is increased by hyaluronic acid; this suggests that intracellular factors are involved. Confocal microscopy experiments demonstrated that extracellular heparan sulfate and hyaluronic acid are taken into cells both with free and DNA-associated carriers. We conclude that extracellular GAGs may alter both the cellular uptake and the intracellular behavior of the DNA complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Contrast Media / pharmacology
  • DNA / metabolism
  • DNA / pharmacokinetics
  • Flow Cytometry
  • Fluorescein / pharmacology
  • Gene Transfer Techniques*
  • Genes, Reporter
  • Genetic Therapy / methods
  • Glycosaminoglycans / physiology*
  • Green Fluorescent Proteins
  • Heparitin Sulfate / pharmacology
  • Hyaluronic Acid / pharmacology
  • Liposomes / chemistry*
  • Luminescent Proteins / metabolism
  • Luminescent Proteins / pharmacokinetics
  • Microscopy, Confocal
  • Plasmids / metabolism
  • Protein Binding
  • Transfection


  • Adjuvants, Immunologic
  • Contrast Media
  • Glycosaminoglycans
  • Liposomes
  • Luminescent Proteins
  • Green Fluorescent Proteins
  • Hyaluronic Acid
  • DNA
  • Heparitin Sulfate
  • Fluorescein