1887

Abstract

Genetically modified cells of haematopoietic and lymphocytic lineages could provide potentially curative treatments for a wide range of inherited and acquired diseases. However, this application is limited in mouse models by the low efficiency of lentiviral vectors. To facilitate the rapid production of high-titre helper-free retroviral vectors for enhanced gene delivery, multiple modifications to a prototype moloney murine leukemia virus (MoMLV)-derived vector system were made including adaptation of the vector system to simian virus 40 /T antigen-mediated episomal replication in packaging cells, replacement of the MoMLV 5′ U3 promoter with a series of stronger composite promoters and addition of an extra polyadenylation signal downstream of the 3′ long terminal repeat. These modifications enhanced vector production by 2–3 logs. High-titre vector stocks were tested for their ability to infect a variety of cells derived from humans and mice, including primary monocyte-derived macrophage cultures. Whilst the lentiviral vector was significantly restricted at the integration level, the MoMLV-based vector showed effective gene transduction of mouse cells. This high-titre retroviral vector system represents a useful tool for efficient gene delivery into human and mouse haematopoietic and lymphocytic cells, with particular application in mice as a small animal model for novel gene therapy tests.

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2010-08-01
2024-03-28
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References

  1. Aiuti A., Cattaneo F., Galimberti S., Benninghoff U., Cassani B., Callegaro L., Scaramuzza S., Andolfi G., Mirolo M. other authors 2009; Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med 360:447–458
    [Google Scholar]
  2. Ayuk F. A., Zander A. R., Fehse B. 2001; T lymphocytes as targets of gene transfer with Moloney-type retroviral vectors. Curr Gene Ther 1:325–337
    [Google Scholar]
  3. Burke B., Sumner S., Maitland N., Lewis C. E. 2002; Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. J Leukoc Biol 72:417–428
    [Google Scholar]
  4. Campbell R. E., Tour O., Palmer A. E., Steinbach P. A., Baird G. S., Zacharias D. A., Tsien R. Y. 2002; A monomeric red fluorescent protein. Proc Natl Acad Sci U S A 99:7877–7882
    [Google Scholar]
  5. Cartier N., Hacein-Bey-Abina S., Bartholomae C. C., Veres G., Schmidt M., Kutschera I., Vidaud M., Abel U., Dal-Cortivo L. other authors 2009; Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326:818–823
    [Google Scholar]
  6. Clay T. M., Custer M. C., Spiess P. J., Nishimura M. I. 1999; Potential use of T cell receptor genes to modify hematopoietic stem cells for the gene therapy of cancer. Pathol Oncol Res 5:3–15
    [Google Scholar]
  7. Cockrell A. S., Kafri T. 2003; HIV-1 vectors: fulfilment of expectations, further advances, and still a way to go. Curr HIV Res 1:419–439
    [Google Scholar]
  8. Culver K., Cornetta K., Morgan R., Morecki S., Aebersold P., Kasid A., Lotze M., Rosenberg S. A., Anderson W. F., Blaese R. M. 1991; Lymphocytes as cellular vehicles for gene therapy in mouse and man. Proc Natl Acad Sci U S A 88:3155–3199
    [Google Scholar]
  9. Donahue R. E., Byrne E. R., Thomas T. E., Kirby M. R., Agricola B. A., Sellers S. E., Gaudernack G., Karisson S., Lansdorp P. M. 1996; Transplantation and gene transfer of the human glucocerebrosidase gene into immunoselected primate CD34+Thy-1+ cells. Blood 88:4166–4172
    [Google Scholar]
  10. Dou H., Destache C. J., Morehead J. R., Mosley R. L., Boska M. D., Kingsley J., Gorantla S., Poluektova L., Nelson J. A. other authors 2006; Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. Blood 108:2827–2835
    [Google Scholar]
  11. Dou H., Grotepas C. B., McMillan J. M., Destache C. J., Chaubal M., Werling J., Kipp J., Rabinow B., Gendelman H. E. 2009; Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of neuroAIDS. J Immunol 183:661–669
    [Google Scholar]
  12. Fischer A., Cavazzana-Calvo M. 2008; Gene therapy of inherited diseases. Lancet 371:2044–2047
    [Google Scholar]
  13. Gough P. J., Raines E. W. 2003; Gene therapy of apolipoprotein E-deficient mice using a novel macrophage-specific retroviral vector. Blood 101:485–491
    [Google Scholar]
  14. Hawley R. G. 2001; Progress toward vector design for hematopoietic stem cell gene therapy. Curr Gene Ther 1:1–17
    [Google Scholar]
  15. Landau N. R., Littman D. R. 1992; Packaging system for rapid production of murine leukemia virus vectors with variable tropism. J Virol 66:5110–5113
    [Google Scholar]
  16. May T., Butueva M., Bantner S., Marcusic D., Seppen J., Weich H., Hauser H., Wirth D. 2009; Synthetic gene regulation circuits for control of cell expansion. Tissue Eng Part A 16:441–452
    [Google Scholar]
  17. McTaggart S., Al-Rubeai M. 2002; Retroviral vectors for human gene delivery. Biotechnol Adv 20:1–31
    [Google Scholar]
  18. Miller J. W. 2008; Preliminary results of gene therapy for retinal degeneration. N Engl J Med 358:2282–2284
    [Google Scholar]
  19. Naldini L. 2009; A comeback for gene therapy. Science 326:805–806
    [Google Scholar]
  20. Noser J. A., Towers G. J., Sakuma R., Dumont J.-M., Collins M. K. L., Ikeda Y. 2006; Cyclosporine increases human immunodeficiency virus type 1 vector transduction of primary mouse cells. J Virol 80:7769–7774
    [Google Scholar]
  21. Okasora T., Jo J. I., Tabata Y. 2008; Augmented anti-tumor therapy through natural targetability of macrophages genetically engineered by NK4 plasmid DNA. Gene Ther 15:524–530
    [Google Scholar]
  22. Pear W. S., Nolan G. P., Scott M. L., Baltimore D. 1993; Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci U S A 90:8392–8396
    [Google Scholar]
  23. Qin X. F., An D. S., Chen I. S., Baltimore D. 2003; Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci U S A 100:183–188
    [Google Scholar]
  24. Roszkowski J. J., Lyons G. E., Kast W. M., Yee C., Van Besien K., Nishimura M. I. 2005; Simultaneous generation of CD8+ and CD4+ melanoma-reactive T cells by retroviral-mediated transfer of a single T-cell receptor. Cancer Res 65:1570–1576
    [Google Scholar]
  25. Schambach A., Mueller D., Galla M., Verstegen M. M. A., Wagemaker G., Loew R., Baum C., Bohne J. 2006; Overcoming promoter competition in packaging cells improves production of self-inactivating retroviral vectors. Gene Ther 13:1524–1533
    [Google Scholar]
  26. Sharova N., Wu Y., Zhu X., Stranska R., Kaushik R., Sharkey M., Stevenson M. 2008; Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS Pathog 4:e1000057
    [Google Scholar]
  27. Soneoka Y., Cannon P. M., Ramsdale E. E., Griffiths J. C., Romano G., Kingsman S. M., Kingsman A. J. 1995; A transient three plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Res 23:628–633
    [Google Scholar]
  28. Wilson H. M., Kluth D. C. 2003; Targeting genetically modified macrophages to the glomerulus. Nephron Exp Nephrol 94:e113–e118
    [Google Scholar]
  29. Wirth J. J., Theisen M. A., Crowle A. J. 1982; Culture conditions required for primary isolation and culture of mouse blood monocytes. J Reticuloendothel Soc 31:325–327
    [Google Scholar]
  30. Wu C., Lu Y. 2007; Inclusion of high molecular weight dextran in calcium phosphate-mediated transfection significantly improves gene transfer efficiency. Cell Mol Biol 53:67–74
    [Google Scholar]
  31. Wu C., Nerurkar V. R., Yanagihara R., Lu Y. 2008; Effective modifications for improved homologous recombination and high-efficiency generation of recombinant adenovirus-based vectors. J Virol Methods 153:120–128
    [Google Scholar]
  32. Zeng L., Yang S., Wu C., Ye L., Lu Y. 2006; Effective transduction of primary mouse blood and bone marrow-derived monocytes/macrophages by HIV-1-based defective lentiviral vectors. J Virol Methods 134:66–73
    [Google Scholar]
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