Targeting an adenoviral gene vector to cytokine-activated vascular endothelium via E-selectin

Gene Ther. 1999 May;6(5):801-7. doi: 10.1038/sj.gt.3300898.

Abstract

We have aimed at selective gene delivery to vascular endothelial cells (EC) at sites of inflammation, by targeting E-selectin, a surface adhesion molecule that is only expressed by activated EC. An anti-E-selectin mAb, 1.2B6, was complexed with the adenovirus vector AdZ.FLAG (expressing the FLAG peptide) by conjugating it to an anti-FLAG mAb. Gene transduction of cultured EC was increased 20-fold compared with AdZ.FLAG complexed with a control bsAb providing EC were activated by cytokines. The anti-E-selectin-complexed vector transduced 29 +/- 9% of intimal EC in segments of pig aorta cultured with cytokines ex vivo, compared with less than 0.1% transduced with the control construct (P < 0.05). This strategy could be developed to target endothelium in inflammation with genes capable of modifying the inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Antibodies, Monoclonal / genetics
  • Aorta
  • Cells, Cultured
  • Cytokines / immunology
  • E-Selectin / immunology*
  • Endothelium, Vascular / metabolism*
  • Gene Expression
  • Gene Targeting / methods
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Lymphocyte Activation
  • Swine
  • Transfection / methods
  • Vasculitis / therapy*

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • E-Selectin