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Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy

Cancer Gene Therapy volume 9, pages 365–371 (2002)Cite this article

Abstract

A main issue for further clinical progress of cancer gene therapy is to develop technologies for efficient and specific delivery of therapeutic genes to tumor cells. In this work, we describe a photochemical treatment that substantially improves gene delivery by adenovirus, one of the most efficient gene delivery vectors known. Transduction of two different cell lines was studied by microscopy, flow cytometry, and an enzymatic assay, employing a β-galactosidase–encoding adenovirus. The photochemical treatment induced a >20-fold increase in gene transduction, compared with conventional adenovirus infection, both when measured as the percentage of cells transduced, and when measured as the total β-galactosidase activity in the cell population. The effect was most pronounced at lower virus doses, where in some cases the same transduction efficiency could be achieved with a 20 times lower virus dose than with conventional infection. Photochemical treatments are already in clinical use for cancer therapy, and generally are very specific and have few side effects. The photochemical internalization technology described thus has a clear potential for improving both the efficiency and the specificity of gene delivery in cancer gene therapy, making it possible to achieve efficient site-specific in vivo gene delivery by adenoviral vectors.

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Acknowledgements

We are very grateful to Dr Frank L Graham for providing the AdHCMV-lacZ adenovirus and to Dr Robin Parks for critically reading the manuscript. The work was supported by the Norwegian Research Council, the Norwegian Cancer Society and the Norwegian Ministry of Health.

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Authors and Affiliations

  1. PCI Biotech AS, Oslo, N-0377, Norway

    Anders Høgset

  2. Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

    Anders Høgset, Birgit Øvstebø Engesæter, Lina Prasmickaite & Kristian Berg

  3. Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

    Birgit Øvstebø Engesæter, Øystein Fodstad & Gunhild Mari Mælandsmo

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  1. Anders Høgset
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  2. Birgit Øvstebø Engesæter
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  3. Lina Prasmickaite
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  4. Kristian Berg
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  5. Øystein Fodstad
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  6. Gunhild Mari Mælandsmo
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Correspondence to Anders Høgset.

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Høgset, A., Øvstebø Engesæter, B., Prasmickaite, L. et al. Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy. Cancer Gene Ther 9, 365–371 (2002). https://doi.org/10.1038/sj.cgt.7700447

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