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Tissue-specific gene therapy directed to tumor angiogenesis

Gene Therapy volume 8, pages 819–827 (2001)Cite this article

Abstract

Gene therapy directed specifically to the vascular wall, particularly to angiogenic endothelial cells is a prerequisite in vascular disease treatment. Angiogenesis is a major feature in many pathological conditions including wound healing, solid tumors, developing metastases, ischemic heart diseases and diabetic retinopathy. In the present study we developed a tissue-specific gene therapy to the angiogenic blood vessels of tumor metastasis using an adeno-based vector containing the murine preproendothelin-1 (PPE-1) promoter. Genes activated by the PPE-1 promoter were highly expressed in bovine aortic endothelial cells in vitro. Systemic injection of the adenoviral vectors AdPPE-1-luciferase and AdCMV-luciferase to normal C57BL/6 mice, resulted in higher activity of PPE-1 promoter compared with CMV promoter in the aorta and vascularized tissues such as heart, kidney, lung and pancreas. Systemic administration of the adenoviral vector, in mice bearing Lewis lung carcinoma, resulted in high and specific activity of PPE-1 in the new vasculature of primary tumors and lung metastasis. Cellular distribution of the delivered gene revealed highest expression of GFP in angiogenic endothelial cells of the metastasis. We expect that this approach of ‘vascular-directed’ gene therapy will be applicable to both vascular diseases and cancer.

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Acknowledgements

We thank Dr J Roitelman for his scientific assistance. This research was supported by the Ministry of Science and Art Fund grant No. 6735195; Israel Cancer Association through the estate of the late Yvon Heymann; Recanati Foundation, Tel-Aviv University grant No. 01370902.

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Authors and Affiliations

  1. Institute of Lipid and Atherosclerosis Research, Sheba Medical Center, Tel-Hashomer, Israel

    N Varda-Bloom, A Shaish, A Gonen, K Levanon, S Greenbereger, H Levkovitz & D Harats

  2. Institute of Endocrinology, Sheba Medical Center, Tel-Hashomer, Israel

    S Ferber

  3. Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel

    D Castel

  4. Institute of Pathology, Sheba Medical Center, Tel-Hashomer, Israel

    I Goldberg, A Afek & Y Kopolovitc

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  1. N Varda-Bloom
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Varda-Bloom, N., Shaish, A., Gonen, A. et al. Tissue-specific gene therapy directed to tumor angiogenesis. Gene Ther 8, 819–827 (2001). https://doi.org/10.1038/sj.gt.3301472

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