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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.020255-0
2010-08-01
2019-11-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/8/1909.html?itemId=/content/journal/jgv/10.1099/vir.0.020255-0&mimeType=html&fmt=ahah

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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [Google Scholar]
  12. Fischer, A. & Cavazzana-Calvo, M. ( 2008; ). Gene therapy of inherited diseases. Lancet 371, 2044–2047.[CrossRef]
    [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.[CrossRef]
    [Google Scholar]
  14. Hawley, R. G. ( 2001; ). Progress toward vector design for hematopoietic stem cell gene therapy. Curr Gene Ther 1, 1–17.[CrossRef]
    [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.[CrossRef]
    [Google Scholar]
  18. Miller, J. W. ( 2008; ). Preliminary results of gene therapy for retinal degeneration. N Engl J Med 358, 2282–2284.[CrossRef]
    [Google Scholar]
  19. Naldini, L. ( 2009; ). A comeback for gene therapy. Science 326, 805–806.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [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 [CrossRef]
    [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.[CrossRef]
    [Google Scholar]
  28. Wilson, H. M. & Kluth, D. C. ( 2003; ). Targeting genetically modified macrophages to the glomerulus. Nephron Exp Nephrol 94, e113–e118.[CrossRef]
    [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.[CrossRef]
    [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.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.020255-0
Loading
/content/journal/jgv/10.1099/vir.0.020255-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error