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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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References

  1. Verma IM, Somia N . Gene therapy — promises, problems and prospect Nature 1997 389: 239–242

    Article  CAS  PubMed  Google Scholar 

  2. Anderson WF . Human gene therapy Nature 1998 392: 25–30

    CAS  PubMed  Google Scholar 

  3. Berg K, Selbo PK, Prasmickaite L et al. Photochemical internalization: a novel technology for delivery of macromolecules into cytosol Cancer Res 1999 59: 1180–1183

    CAS  PubMed  Google Scholar 

  4. Høgset A, Prasmickaite L, Tjelle TE, Berg K . Photochemical transfection: a new technology for light-induced, site-directed gene delivery Hum Gene Ther 2000 11: 869–880

    Article  PubMed  Google Scholar 

  5. Selbo PK, Sivam G, Fodstad Ø, Sandvig K, Berg K . Photochemical internalisation increases the cytotoxic effect of the immunotoxin MOC31-gelonin Int J Cancer 2000 87: 853–859

    Article  CAS  PubMed  Google Scholar 

  6. Selbo PK, Sandvig K, Kirveliene V, Berg K . Release of gelonin from endosomes and lysosomes to cytosol by photochemical internalization Biochim Biophys Acta 2000 1475: 307–313

    Article  CAS  PubMed  Google Scholar 

  7. Prasmickaite L, Høgset A, Berg K . Evaluation of different photosensitizers for use in photochemical gene transfection Photochem Photobiol 2001 73: 388–395

    Article  CAS  PubMed  Google Scholar 

  8. Prasmickaite L, Høgset A, Tjelle TE, Olsen VM, Berg K . The role of endosomes in gene transfection mediated by photochemical internalisation J Gene Med 2000 2: 477–488

    Article  CAS  PubMed  Google Scholar 

  9. Høgset A, Prasmickaite L, Hellum M et al. Photochemical transfection; a technology for efficient light directed gene delivery In: Saltzman WM, Luo D, eds Synthetic DNA Delivery Systems Austin: Landes Bioscience Publishers 2002

    Google Scholar 

  10. Dash PR, Read ML, Barrett LB, Wolfert MA, Seymour LW . Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery Gene Ther 1999 6: 643–650

    Article  CAS  PubMed  Google Scholar 

  11. Nemerow GR, Stewart PL . Role of alpha(v) integrins in adenovirus cell entry and gene delivery Microbiol Mol Biol Rev 1999 63: 725–734

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Leopold PL, Kreitzer G, Miyazawa N et al. Dynein- and microtubule-mediated translocation of adenovirus serotype 5 occurs after endosomal lysis Hum Gene Ther 2000 11: 151–165

    Article  CAS  PubMed  Google Scholar 

  13. Greber UF, Willetts M, Webster P, Helenius A . Stepwise dismantling of adenovirus 2 during entry into cells Cell 1993 75: 477–486

    Article  CAS  PubMed  Google Scholar 

  14. Leopold PL, Ferris B, Grinberg I, Worgall S, Hackett NR, Crystal RG . Fluorescent virions: dynamic tracking of the pathway of adenoviral gene transfer vectors in living cells Hum Gene Ther 1998 9: 367–378

    Article  CAS  PubMed  Google Scholar 

  15. Hansen J, Qing K, Kwon HJ, Mah C, Srivastava A . Impaired intracellular trafficking of adeno-associated virus type 2 vectors limits efficient transduction of murine fibroblasts JVirol 2000 74: 992–996

    Article  CAS  Google Scholar 

  16. Hitt M, Bett AJ, Addison CL, Prevec L, Graham FL . Techniques for human adenovirus vector construction and characterization Methods Mol Genet 1995 7: 13–30

    Article  CAS  Google Scholar 

  17. Cantwell MJ, Sharma S, Friedmann T, Kipps TJ . Adenovirus vector infection of chronic lymphocytic leukemia B cells Blood 1996 88: 4676–4683

    CAS  PubMed  Google Scholar 

  18. Tang D-C, Jennelle RS, Shi Z, Garver RI Jr, Carbone DP, Loya F, Chang C-H, Curiel DT . Overexpression of adenovirus-encoded transgenes from the cytomegalovirus immediate early promoter in irradiated tumor cells Hum Gene Ther 1997 8: 2117–2124

    Article  CAS  PubMed  Google Scholar 

  19. Wickham TJ . Targeting adenovirus Gene Ther 2000 7: 110–114

    Article  CAS  PubMed  Google Scholar 

  20. Miller N, Whelan J . Progress in transcriptionally targeted and regulatable vectors for genetic therapy Hum Gene Ther 1997 8: 803–815

    Article  CAS  PubMed  Google Scholar 

  21. Alemany R, Balague C, Curiel DT . Replicative adenoviruses for cancer therapy Nat Biotechnol 2000 18: 723–727

    Article  CAS  PubMed  Google Scholar 

  22. Dougherty TJ, Gomer CJ, Henderson BW et al. Photodynamic therapy J Natl Cancer Inst 1998 90: 889–905

    Article  CAS  PubMed  Google Scholar 

  23. Selbo PK, Sivam G, Fodstad Ø, Sandvig K, Berg K . In vivo documentation of photochemical internalization, a novel approach to site specific cancer therapy Int J Cancer 2001 92: 761–766

    Article  CAS  PubMed  Google Scholar 

  24. Pass HI . Photodynamic therapy in oncology: mechanisms and clinical use J Natl Cancer Inst 1993 85: 443–456

    Article  CAS  PubMed  Google Scholar 

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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

Authors
  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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  • DOI: https://doi.org/10.1038/sj.cgt.7700447

Keywords

  • adenovirus
  • gene therapy
  • photodynamic
  • photochemical
  • endosomes

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