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A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E

Gene Therapy volume 6, pages 1153–1159 (1999)Cite this article

Abstract

A major focus in gene therapy has been the use of recombinant viruses to deliver genes in vivo. Although this approach shows much promise, there are many safety concerns associated with the use of viral materials in the treatment of human diseases. Our alternative cell-based gene therapy approach utilizes endothelial cells (Pro 175) isolated from the murine embryonic yolk sac. These endothelial cells were evaluated for their potential use in gene therapy as a gene delivery platform. As a test model, we used these cells to deliver apolipoprotein E (apoE) in the murine apoE knockout atherosclerosis model. The lack of apoE protein in these animals results in high levels of serum cholesterol and formation of severe aortic plaques and lesions at a young age. After transplantation of the apoE secreting Pro 175 endothelial cells into apoE-deficient mice, serum cholesterol levels were measured at 2 week intervals. During the 3 months after the initiation of these experiments, levels of cholesterol in the animals having received the apoE secreting endothelial cells were statistically lower compared with the levels of age-matched controls having received non-secreting endothelial cells. Concomitant with cholesterol reduction, atherosclerotic aortic plaques were noticeably reduced in the experimental apoE+ animals. These results highlight the potential of these unique endothelial cells as an efficient delivery platform for somatic gene therapy.

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Acknowledgements

The excellent technical assistance of Jay Erisman and Viy McGauhy is gratefully acknowledged. We would like to thank Dr Joseph Cioffi for carefully reviewing the manuscript. We would like to thank Dr Alan Attie for his generous gift of the human apoE3 gene.

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Author notes

  1. L Cioffi and F G Sturtz: The two first authors have equally contributed to this study

Authors and Affiliations

  1. Progenitor, Inc., Menlo Park, CA, USA

    L Cioffi, F G Sturtz, S Wittmer, B Barut, J Smith-Gbur, V Moore, T Zupancic & H R Snodgrass

  2. Department of Zoology, University of Wisconsin, Madison, WI, USA

    B Gilligan & R Auerbach

  3. Biostatistics Department, Centre Anticancéreux Léon Bérard, Lyon, France

    F Gomez & F Chauvin

  4. University of Colorado at Boulder, Boulder, CO, USA

    M Antczak

  5. Ontogeny, Inc., Cambridge, MA, USA

    D Platika

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  1. L Cioffi
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  2. F G Sturtz
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  3. S Wittmer
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  4. B Barut
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  6. V Moore
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  7. T Zupancic
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  10. F Gomez
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  14. H R Snodgrass
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Cioffi, L., Sturtz, F., Wittmer, S. et al. A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E. Gene Ther 6, 1153–1159 (1999). https://doi.org/10.1038/sj.gt.3300890

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  • DOI: https://doi.org/10.1038/sj.gt.3300890

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