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

Gene Therapy volume 6, pages 801–807 (1999)Cite this article

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.

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Authors and Affiliations

  1. BHF Cardiovascular Medicine Unit, National Heart and Lung Institute, Imperial College School of Medicine, London, UK

    O A Harari, C J Stocker, T Y Huehns & D O Haskard

  2. Department of Histopathology, Hammersmith Hospital, Imperial College School of Medicine, London, UK

    C Sarraf

  3. Genvec Inc, Rockville, MD, USA

    T J Wickham & I Kovesdi

  4. National Cancer Institute, Experimental Immunology, Bethesda, MD, USA

    D M Segal

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  1. O A Harari
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  2. T J Wickham
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  4. I Kovesdi
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  5. D M Segal
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  8. D O Haskard
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Harari, O., Wickham, T., Stocker, C. et al. Targeting an adenoviral gene vector to cytokine-activated vascular endothelium via E-selectin. Gene Ther 6, 801–807 (1999). https://doi.org/10.1038/sj.gt.3300898

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  • DOI: https://doi.org/10.1038/sj.gt.3300898

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