Retroviral Vectors for Suicide Gene Therapy

  • Colin Porter
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 90)

Abstract

A recombinant retroviral vector is one of many available options for effecting gene transfer. To date, this type of vector has been most widely used and is involved in more than a third of current gene therapy trials, many of which are for delivery of suicide genes in the context of cancer treatment (1). Many issues that may impinge upon the choice of vector are specific to individual applications. However, in general, retroviral vectors may be chosen for reasons of their relatively high efficiency of gene delivery, the stable integration of the transgene delivered, and their immunological “silence.” A distinction exists between vectors based on murine leukemia virus (MLV) and those derived from lentiviruses, such as human immunodeficiency virus (HIV). MLV vector gene delivery is restricted to proliferating target cells (2), resulting from a requirement for breakdown of the nuclear membrane, whereas HIV vectors can additionally infect nondividing cells. Lentiviral vectors are in their relative infancy and will not be considered further in this chapter. Depending on the proposed application, it will be necessary to consider whether this proliferation requirement for MLV vectors is advantageous or not. Efficacy shown by several of the suicide enzyme/prodrug systems, such as HSV thymidine kinase (HSV-TK) and gancyclovir, is similarly dependent on cell proliferation.

Keywords

Filtration Phenol Manifold EDTA Recombination 

References

  1. 1.
  2. 2.
    Miller, D. G., Adam, M. A., and Miller, A. D. (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol. Cell Biol. 10, 4239–4242.PubMedGoogle Scholar
  3. 3.
    Collins, M. K. L. and Porter, C. D. (1999) Retroviral vectors, in Blood Cell Biochemistry Volume 8: Hematopoiesis and Gene Therapy (Fairbairn, L. J. and Testa, N. G., eds.), Kluwer Academic/Plenum, New York, pp. 57–88.Google Scholar
  4. 4.
    Emerman, M. and Temin, H. (1984) Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell 39, 459–467.CrossRefGoogle Scholar
  5. 5.
    Takeuchi, Y., Cosset, F.-L., Lachmann, P. J., Okada, H., Weiss, R. A., and Collins, M. K. L. (1994) Type C retrovirus inactivation by human complement is determined by both the viral genome and producer cell. J. Virol. 68, 8001–8007.PubMedGoogle Scholar
  6. 6.
    Porter, C. D., Collins, M. K. L., Tailor, C. S., et al. (1996) Comparison of efficiency of infection of human gene therapy target cells via four different retroviral receptors. Hum. Gene Ther. 7, 913–919.PubMedCrossRefGoogle Scholar
  7. 7.
    Emi, N., Friedmann, T., and Yee, J. K. (1991) Pseudotype formation of murine leukaemia virus with the G protein of vesicular stomatitis virus. J. Virol. 65, 1202–1207.PubMedGoogle Scholar
  8. 8.
    Markowitz, D., Goff, S., and Bank, A. (1988) A safe packaging line for gene transfer: separating viral genes on two different plasmids. J. Virol. 82, 1120–1124.Google Scholar
  9. 9.
    Morgenstern, J. P. and Land, H. (1990) Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res. 18, 3587–3596.PubMedCrossRefGoogle Scholar
  10. 10.
    Miller, A. D. and Rosman, G. J. (1989) Improved retroviral vectors for gene transfer and expression. BioTechniques 7, 980–990.PubMedGoogle Scholar
  11. 11.
    Ohashi, T., Boggs, S., Robbins, P., et al. (1992) Efficient transfer and sustained high expression of the human glucocerebrosidase gene in mice and their functional macrophages following transplantation of bone marrow transduced by a retroviral vector. Proc. Natl. Acad. Sci. USA 89, 11,332–11,336.PubMedCrossRefGoogle Scholar
  12. 12.
    Miller, A. D. and Buttimore, C. (1986) Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol. Cell. Biol. 6, 2895–2902.PubMedGoogle Scholar
  13. 13.
    Markowitz, D., Goff, S., and Bank, A. (1988) Construction and use of a safe and efficient amphotropic packaging cell line. Virology 167, 400–406.PubMedGoogle Scholar
  14. 14.
    Miller, A. D., Garcia, J. V., Suhr, N. V., Lynch, C. M., Wilson, C., and Eiden, M. V. (1991) Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus. J. Virol. 65, 2220–2224.PubMedGoogle Scholar
  15. 15.
    Cosset, F.-L., Takeuchi, Y., Battini, J. L., Weiss, R. A., and Collins, M. K. L. (1995) High titre packaging cells producing recombinant retroviruses resistant to human serum. J. Virol. 69, 7430–7436.PubMedGoogle Scholar
  16. 16.
    Miller, A. and Chen, F. (1996) Retrovirus packaging cells based on 10A1 murine leukemia virus for production of vectors that use multiple receptors for cell entry. J. Virol. 70, 5564–5571.PubMedGoogle Scholar
  17. 17.
  18. 18.
    Strair, R. K., Towle, M. J., and Smith, B. R. (1988) Recombinant retroviruses encoding cell surface antigens as selectable markers. J. Virol. 62, 4756–4759.PubMedGoogle Scholar
  19. 19.
    Slingsby, J. H., Baban, D., Sutton, J., et al. (2000) Analysis of 4070A envelope levels in retroviral preparations and effect on target cell transduction efficiency. Hum. Gene Ther. 11, 1439–1451.PubMedCrossRefGoogle Scholar
  20. 20.
    Mavria, G. and Porter, C. D. (2001) Reduced growth in response to ganciclovir treatment of subcutaneous xenografts expressing HSV-tk in the vascular compartment. Gene Ther. 8, 913–920.PubMedCrossRefGoogle Scholar
  21. 21.
    Hurford, R. K., Dranoff, G., Mulligan, R. C., and Tepper, R. I. (1995) Gene therapy of metastatic cancer by in vivo gene targeting. Nature Genet. 10, 430–435.PubMedCrossRefGoogle Scholar
  22. 22.
    Ram, Z., Culver, K. W., Walbridge, S., Blaese, R. M., and Oldfield, E. H. (1993) In situ retroviral-mediated gene transfer for the treatment of brain tumours in rats. Cancer Res. 53, 83–88.PubMedGoogle Scholar
  23. 23.
    Russell, S. J., and Cosset, F.-L. (1999) Modifying the host range properties of retroviral vectors. J. Gene Med. 1, 300–311.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Colin Porter
    • 1
  1. 1.Section of Cell and Molecular Biology at the Institute of Cancer ResearchLondonUK

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