Tissue-specific gene therapy directed to tumor angiogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2001-06

AUTHORS

N Varda-Bloom, A Shaish, A Gonen, K Levanon, S Greenbereger, S Ferber, H Levkovitz, D Castel, I Goldberg, A Afek, Y Kopolovitc, D Harats

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. More... »

PAGES

3301472

Journal

TITLE

Gene Therapy

ISSUE

11

VOLUME

8

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.gt.3301472

    DOI

    http://dx.doi.org/10.1038/sj.gt.3301472

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1030906111

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11423929


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