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Intercellular delivery of thymidine kinase prodrug activating enzyme by the herpes simplex virus protein, VP22

Gene Therapy volume 6, pages 12–21 (1999)Cite this article

Abstract

We demonstrate that fusion proteins consisting of the herpes simplex virus (HSV) transport protein VP22 linked in frame to HSV thymidine kinase (tk) retain the ability to be transported between cells. In vivo radiolabelling experiments and in vitro assays show that the fusion proteins also retain tk activity. When transfected COS cells, acting as a source of the VP22-tk chimera, were co-plated on to gap junction-negative neuroblastoma cells, ganciclovir treatment induced efficient cell death in the recipient neuroblastoma cell monolayer. No such effect was observed with COS cells transfected with tk alone. Tumours established in mice with neuroblastoma cell lines expressing VP22-tk regressed upon administration of ganciclovir. Furthermore tumours established from 50:50 mixtures of VP22-tk transduced and nontransduced cells also regressed while no significant effect was observed in similar experiments with cells transduced with tk alone. VP22 mediated transport may thus have application in a clinical setting to amplify delivery of the target protein in enzyme-prodrug protocols.

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Author notes

  1. M S Dilber and A Phelan: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Medicine, Karolinska Institute, NOVUM, Huddinge, Sweden

    M S Dilber & A Aints

  2. Department of Gene Therapy Research Centre, Clinical Research Centre, Huddinge Hospital, Karolinska Institute NOVUM, Huddinge, Sweden

    M S Dilber & CI Edvard Smith

  3. Department of Biosciences, Center for BioTechnology, Karolinska Institute, NOVUM, Huddinge

    M S Dilber, A Aints, A J Mohamed & CI Edvard Smith

  4. Marie Curie Research Institute, Oxted, UK

    A Phelan, G Elliott & P O’Hare

  5. Department of Clinical Immunology, Microbiology, Pathology and Infectious Diseases, Karolinska Institute, NOVUM, Huddinge, Sweden

    A J Mohamed & CI Edvard Smith

  6. University College of South Stockholm, Huddinge, Sweden

    A J Mohamed

Authors
  1. M S Dilber
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  2. A Phelan
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  5. G Elliott
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  6. CI Edvard Smith
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  7. P O’Hare
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Dilber, M., Phelan, A., Aints, A. et al. Intercellular delivery of thymidine kinase prodrug activating enzyme by the herpes simplex virus protein, VP22. Gene Ther 6, 12–21 (1999). https://doi.org/10.1038/sj.gt.3300838

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  • DOI: https://doi.org/10.1038/sj.gt.3300838

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