Human Immunodeficiency Virus Type 1-Based Vectors for Gene Delivery to Human Hematopoietic Stem Cells

  • Ali Ramezani
  • Robert G. Hawley
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 76)


A number of inherited and acquired disorders can potentially be treated by gene-based therapies. To be successful, gene therapy requires efficient delivery and continued expression of the therapeutic gene in the target cell. Toward this goal, a variety of methods have been developed for delivering genes into various cell types and tissues (for reviews, see refs. 1 and 2). Common viralbased methods utilize vectors derived from oncoretroviruses, adenovirus type 5, adenoassociated virus type 2, herpes simplex virus type 1 (HSV-1), and, most recently, lentiviruses. Among these, oncoretroviral vectors (primarily those based on Moloney murine leukemia virus) have been the most widely used to date in gene therapy applications, mainly because of their capacity to stably integrate into cellular DNA in the absence of wild-type virus (3, 4, 5). However, a major limitation of oncoretroviral vectors is their inability to transduce nondividing cells (6, 7, 8, 9).


Invitrogen Corporation Equine Infectious Anemia Virus Vector Particle Human Embryonic Kidney 293T Cell Vector Titer 
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  1. 1.
    Lollo, C. P., Banaszczyk, M. G., and Chiou, H. C. (2000) Obstacles and advances in non-viral gene delivery. Curr. Opin. Mol. Ther. 2, 136–142.PubMedGoogle Scholar
  2. 2.
    Kay, M. A., Glorioso, C. J., and Naldini, L. (2001) Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat. Med. 7, 33–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Miller, A. D. (1992) Retroviral vectors. Curr. Top. Microbiol. Immunol. 158,1–24.PubMedCrossRefGoogle Scholar
  4. 4.
    Miller, A. D., Miller, D. G., Garcia, J. V., and Lynch, C. M. (1993) Use of retroviral vectors for gene transfer and expression. Methods Enzymol. 217,581–599.PubMedCrossRefGoogle Scholar
  5. 5.
    Hawley, R. G. (1996) Therapeutic potential of retroviral vectors. Transfus. Sci. 17,7–14.CrossRefGoogle Scholar
  6. 6.
    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
  7. 7.
    Roe, T., Reynolds, T. C., Yu, G., and Brown, P. O. (1993) Integration of murine leukemia virus DNA depends on mitosis. EM BO J. 12, 2099–2108.Google Scholar
  8. 8.
    Lewis, P. F. and Emerman, M. (1994) Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J. Virol. 68, 510–516.PubMedGoogle Scholar
  9. 9.
    Lewis, P., Hensel, M., and Emerman, M. (1992) Human immunodeficiency virus infection of cells arrested in the cell cycle. EMBO J. 11, 3053–3058.PubMedGoogle Scholar
  10. 10.
    Poeschla, E., Gilbert, J., Li, X., Huang, S., Ho, A., and Wong-Staal, F. (1998) Identification of a human immunodeficiency virus type 2 (HIV-2) encapsidation determinant and transduction of nondividing human cells by HIV-2-based lentiviral vectors. J. Virol. 72,6527–6536.PubMedGoogle Scholar
  11. 11.
    Kim, S. S., Kothari, N., You, X. J., Robinson, W. E. Jr., Schnell, T., Uberla, K., et al. (2001) Generation of replication-defective helper-free vectors based on simian immunodeficiency virus. Virology 282,154–167.PubMedCrossRefGoogle Scholar
  12. 12.
    Curran, M. A., Kaiser, S. M., Achacoso, P. L., and Nolan, G. P. (2000) Efficient transduction of nondividing cells by optimized feline immunodeficiency virus vectors. Mol. Ther. 1, 31–38.PubMedCrossRefGoogle Scholar
  13. 13.
    Mitrophanous, K., Yoon, S., Rohll, J., Patil, D., Wilkes, F., Kim, V., et al. (1999) Stable gene transfer to the nervous system using a non-primate lentiviral vector. Gene Ther. 6,1808–1818.PubMedCrossRefGoogle Scholar
  14. 14.
    Berkowitz, R. D., Ilves, H., Plavec, I., and Veres, G. (2001) Gene transfer systems derived from Visna virus: analysis of virus production and infectivity. Virology 279,116–129.PubMedCrossRefGoogle Scholar
  15. 15.
    Frankel, A. D. and Young, J. A. (1998) HIV-1: fifteen proteins and an RNA. Annu. Rev. Biochem. 67,1–25.PubMedCrossRefGoogle Scholar
  16. 16.
    Schwartz, S., Felber, B. K., and Pavlakis, G. N. (1992) Distinct RNA sequences in the gag region of HIV-1 decrease RNA stability and inhibit expression in the absence of Rev protein. J. Virol. 66, 150–159.PubMedGoogle Scholar
  17. 17.
    Rosen, C. A., Terwilliger, E., Dayton, A., Sodroski, J. G., and Haseltine, W. A. (1988) Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 85, 2071–2075.PubMedCrossRefGoogle Scholar
  18. 18.
    Lever, A., Gottlinger, H., Haseltine, W., and Sodroski, J. (1989) Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J. Virol. 63,4085–4087.PubMedGoogle Scholar
  19. 19.
    Richardson, J. H., Child, L. A., and Lever, A. M. (1993) Packaging of HIV-1 RNA requires cis-acting sequences outside the 5 leader region. J. Virol. 67, 3997–4005.PubMedGoogle Scholar
  20. 20.
    Maddon, P. J., Dalgleish, A. G., McDougal, J. S., Clapham, P. R., Weiss, R. A., and Axel, R. (1986) The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47, 333–348.PubMedCrossRefGoogle Scholar
  21. 21.
    Dalgleish, A. G., Beverley, P. C. L., Clapham, P. R., Crawford, D. H., Greaves M. F., and Weiss, R. A. (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312,763–767.PubMedCrossRefGoogle Scholar
  22. 22.
    Hill C. M., Deng, H., Unutmaz, D., Kewalramani, V. N., Bastiani, L., Gorny, M. K, et al. (1997) Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor. J. Virol. 71,6296–6304.PubMedGoogle Scholar
  23. 23.
    Bandres, J. C., Wang, Q. F., O’Leary, J., Baleaux, F., Amara, A., Hoxie, J. A., et al. (1998) Human immunodeficiency virus (HIV) envelope binds to CXCR4 independently of CD4 and binding can be enhanced by interaction with soluble CD4 or by HIV-1 envelope deglycosylation. J. Virol. 72, 2500–2504.PubMedGoogle Scholar
  24. 24.
    Alkhatib, G., Combardiere, C., Broder, C. C., Feng, Y., Kennedy, P. E., Murphy, P. M., et al. (1996) CC CKR5: A RANTES, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272, 1955–1958.PubMedCrossRefGoogle Scholar
  25. 25.
    Choe, H., Farzan, M., Sun, Y., Sullivan, N., Rollins, B., Ponath, P. D., et al. (1996) The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85,1135–1148.PubMedCrossRefGoogle Scholar
  26. 26.
    Feng, Y., Broder, C. C., Kennedy, P. E., and Berger, E. A. (1996) HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872–877.PubMedCrossRefGoogle Scholar
  27. 27.
    Goff, S. P. (1990) Retroviral RT: synthesis, structure and function. J. Acquir. Immune Defic. Syndr. 3, 817–831.PubMedGoogle Scholar
  28. 28.
    Farnet, C. M. and Haseltine, W. A. (1991) Determination of viral proteins present in HIV-1 pre-integration complex. J. Virol. 65,1910–1915.PubMedGoogle Scholar
  29. 29.
    Bukrinsky, M. I., Sharova, N., McDonald, T. L., Pushkarskaya, T., Tarpley, W. G., and Stevenson, M. (1993) Association of IN, MA and RT antigens of HIV-1 with viral nucleic acids following acute infection. Proc. Natl. Acad. Sci. USA 90,6125–6129.PubMedCrossRefGoogle Scholar
  30. 30.
    Bukrinsky, M. I., Haggerty, S., Dempsey, M. P., Sharova, N., Adzhubel, A., et al. (1993) A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365,666–669.PubMedCrossRefGoogle Scholar
  31. 31.
    Gallay, P., Chin, D., Hope, T. J., and Trono, D. (1997) HIV-1 infection of nondividing cells mediated through the recognition of integrase by the import/karyopherin pathway. Proc. Natl. Acad. Sci. USA 94, 9825–9830.PubMedCrossRefGoogle Scholar
  32. 32.
    Heinzinger, N. K., Bukrinsky, M. I., Haggerty, S. A., Ragland, A. M., Kewalramani, V., Lee, M. A., et al. (1994) The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc. Natl. Acad. Sci. USA 91,7311–7315.PubMedCrossRefGoogle Scholar
  33. 33.
    Trono, D. (1995) HIV-1 accessory proteins: Leading roles for the supporting cast. Cell 82,189–192.PubMedCrossRefGoogle Scholar
  34. 34.
    LaFemina, R. L., Callahan, P. L., and Cordingley, M. G. (1990) Substrate specificity of recombinant HIV-1 IN protein. J. Virol. 65,5624–5630.Google Scholar
  35. 35.
    Bushman, F. D. and Craigie, R. (1991) Activities of HIV-1 integration protein in vitro: specific cleavage and integration of HIV-1 DNA. Proc. Natl. Acad. Sci. USA 88,1339–1343.PubMedCrossRefGoogle Scholar
  36. 36.
    Cullen, B. R. (1991) Regulation of HIV-1 gene expression. FASEB J. 5, 2361–2368.PubMedGoogle Scholar
  37. 37.
    Valsamakis, A., Zeichner, S., Carswell, S., and Alwine, J. C. (1991) The HIV-1 polyadenylation signal: a 3 long terminal repeat element upstream of the AAUAAA necessary for efficient polyadenylation. Proc. Natl. Acad. Sci. USA 88,2108–2112.PubMedCrossRefGoogle Scholar
  38. 38.
    Feng, S. and Holland, E. C. (1988) HIV-1 tat trans-activation requires the loop sequence within tar. Nature 334,165–167.PubMedCrossRefGoogle Scholar
  39. 39.
    Keen, N. J., Gait, M. J., and Karn, J. (1996) Human immunodeficiency virus type-1 Tat is an integral component of the activated transcription-elongation complex. Proc. Natl. Acad. Sci. USA 93,2505–2510.PubMedCrossRefGoogle Scholar
  40. 40.
    Daly, T. J., Cook, K. S., Gray, G. S., Maione, T. E., and Rusche, J. R. (1989) Specific binding of HIV-1 recombinant Rev protein to the Rev-response element in vitro. Nature 342, 816–819.PubMedCrossRefGoogle Scholar
  41. 41.
    Fischer, U., Huber, J., Boelens, W. C., Mattaj, I. W., and Lührman, R. (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82,475–483.PubMedCrossRefGoogle Scholar
  42. 42.
    Wen, W., Meinkoth, J. L., Tsien, R. Y., and Taylor, S. S. (1995) Identification of a signal for rapid export of proteins from the nucleus. Cell 82,463–473.PubMedCrossRefGoogle Scholar
  43. 43.
    Ullman, K. S., Powers, M. A., and Forbes, D. J. (1997) Nuclear export receptors: From importin to exportin. Cell 90,967–970.PubMedCrossRefGoogle Scholar
  44. 44.
    Robey, W. G., Safai, B., Oroszlan, S., Arthur, L. O., Gonda, M. A., Gallo, R. C., et al. (1985) Characterization of Env and core structural gene products of HTLV-III with sera from AIDS patients. Science 228,593–595.PubMedCrossRefGoogle Scholar
  45. 45.
    Stein, B. S. and Engleman, E. G. (1990) Intracellular processing of the gp160 HIV-1 Env precursor: endoproteolytic cleavage occurs in a cis or medial compartment of the Golgi complex. J. Biol. Chem. 265, 2640–2649.PubMedGoogle Scholar
  46. 46.
    Freed, E. O., Myers, D. J., and Risser, R. J. (1989) Mutational analysis of the cleavage sequence of the HIV-1 Env glycoprotein precursor gp160. J. Virol. 63, 4670–4675.PubMedGoogle Scholar
  47. 47.
    Bryant, M. and Ranter, L. (1990) Myristylation dependent replication and assembly of HIV-1. Proc. Natl. Acad. Sci. USA 87,523–527.PubMedCrossRefGoogle Scholar
  48. 48.
    Peng, C., Ho, B. K., Chang, T. W., and Chang, N. T. (1989) Role of HIV-1 specific PR in core protein maturation and viral infectivity. J. Virol. 63, 2550–2556.PubMedGoogle Scholar
  49. 49.
    Sheng, N. and Erickson-Viitanen, S. (1984) Cleavage of p15 protein in vitro by HIV-1 PR is RNA dependent. J. Virol. 68,6207–6214.Google Scholar
  50. 50.
    Debouck, C. (1991) Substrate specificity of the human (type 1) and simian immunodeficiency virus proteases. Adv. Exp. Med. Biol. 306, 407–415.PubMedGoogle Scholar
  51. 51.
    Naldini, L., Blomer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., et al. (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263–267.PubMedCrossRefGoogle Scholar
  52. 52.
    Kavanaugh, M. P., Miller, D. G., Zhang, W., Law, W., Kozak, S. L., Kabat, D., et al. (1994) Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retro virus are inducible sodium-dependent phosphate symporters. Proc. Natl. Acad. Sci. USA 91, 7071–7075.PubMedCrossRefGoogle Scholar
  53. 53.
    Schlegel, R., Tralka, T. S., Willingham, M. C., and Pastan, I. (1983) Inhibition of VSV binding and infectivity by phosphatidylserine: Is phosphatidylserine a VSV-binding site? Cell 32 639–646.PubMedCrossRefGoogle Scholar
  54. 54.
    Mastromarino, P., Conti, C., Goldoni, P., Hauttecoeur, B. and Orsi, N. (1987) Characterization of membrane components of the erythrocyte involved in vesicular stomatitis virus attachment and fusion at acidic pH. J. Gen. Virol. 68, 2359–2369.PubMedCrossRefGoogle Scholar
  55. 55.
    Burns, J. C., Friedmann, T., Driever, W., Burrascano, M., and Yee, J. K. (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors. Concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc. Natl. Acad. Sci. USA 90, 8033–8037.PubMedCrossRefGoogle Scholar
  56. 56.
    Page, K. A., Landau, N. R., and Littman, D. R. (1990) Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J. Virol. 64,5270–5276.PubMedGoogle Scholar
  57. 57.
    Landau, N. R., Page, K. A., and Littman, D. R. (1991) Pseudotyping with human T-cell leukemia virus type 1 broadens the human immunodeficiency virus host range. J. Virol. 65, 162–169.PubMedGoogle Scholar
  58. 58.
    Poznansky, M., Lever, A., Begeron, L., Haseltine, W., and Sodroski, J. (1991) Gene transfer into human lymphocytes by a defective human immunodeficiency virus type I vector. J. Virol. 65, 532–536.PubMedGoogle Scholar
  59. 59.
    Buchschacher, G. L. and Panganiban A.T. (1992) Human immunodeficiency virus vectors for inducible expression of foreign genes. J. Virol. 66, 2731–2739.PubMedGoogle Scholar
  60. 60.
    Parolin, C., Dorfman, T., Palu, G., Gottlinger, H., and Sodroski, J0. (1994) Analysis in human immunodeficiency virus type 1 vectors of cis-acting sequences that affect gene transfer into human lymphocytes. J. Virol. 68, 3888–3895.PubMedGoogle Scholar
  61. 61.
    DuBridge, R. B., Tang, P., Hsia, H. C., Leong, P. M., Miller, J. H., and Calos, M. P. (1987) Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system. Mol. Cell. Biol. 7, 379–387.PubMedGoogle Scholar
  62. 62.
    Sun, Y., Pinchuck, L. M., Agy, M. B., and Clark E. A. (1997) Nuclear import of HIV-1 DNA in resting CD4+T cells requires a cyclosporin A-sensitive pathway. J. Immunol. 158,512–517.PubMedGoogle Scholar
  63. 63.
    Korin, Y. D. and Zack, J. A. (1998) Progression to the G1b phase of the cell cycle is required for completion of human immunodeficiency virus type 1 reverse transcription in T cells. J. Virol. 72, 3161–3168.PubMedGoogle Scholar
  64. 64.
    Zufferey, R., Nagy, D., Mandel, R. J., Naldini, L., and Trono, D. (1997) Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat. Biotechnol. 15,871–875.PubMedCrossRefGoogle Scholar
  65. 65.
    Kafri, T., Bloer, U., Peterson, D. A., Gage, F. H., and Verma, I. M. (1997) Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat. Genet. 17,314–317.PubMedCrossRefGoogle Scholar
  66. 66.
    Gasmi, M., Glynn, J., Jin, M. J., Jolly, D. J., Yee, J. K., and Chen, S. T. (1999) Requirements for efficient production and transduction of human immunodeficiency virus type 1-based vectors. J. Virol. 73,1828–1834.PubMedGoogle Scholar
  67. 67.
    Chinnasamy, D., Chinnasamy, N., Enriquez, M. J., Otsu, M., Morgan, R. A., and Candotti, F. (2000) Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Blood 96,1309–1316.PubMedGoogle Scholar
  68. 68.
    Kim, V. N., Mitrophanous, K., Kingsman, S. M., and Kingsman, A. J. (1998) Minimal requirement for a lentivirus vector based on human immunodeficiency virus type 1. J. Virol. 72, 811–816.PubMedGoogle Scholar
  69. 69.
    Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D., et al. (1998) A third-generation lentivirus vector with a conditional packaging system. J. Virol. 72,8463–8471.PubMedGoogle Scholar
  70. 70.
    Miyoshi, H., Blomer, U., Takahashi, M., Gage, F. H., and Verma, I. M. (1998) Development of a self-inactivating lentivirus vector. J. Virol. 72, 8150–8157.PubMedGoogle Scholar
  71. 71.
    Zufferey, R., Dull, T., Mandel, R. J., Bukovsky, A., Quiroz, D., Naldini, L., et al. (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J. Virol. 72,9873–9880.PubMedGoogle Scholar
  72. 72.
    Zennou, V., Petit, C., Guetard, D., Nerhbass, U., Montagnier, L., and Charneau, P. (2000) HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101,173–185.PubMedCrossRefGoogle Scholar
  73. 73.
    Follenzi, A., Ailles, L. E., Bakovic, S., Geuna, M., and Naldini, L. (2000) Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nature Genet. 25,217–222.PubMedCrossRefGoogle Scholar
  74. 74.
    Bray, M., Prasad, S., Dubay, J. W., Hunter, E., Jeang, K. T., Rekosh, D., et al. (1994) A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc. Natl. Acad. Sci. USA 91, 1256–1260.PubMedCrossRefGoogle Scholar
  75. 75.
    Ernst, R. K., Bray, M., Rekosh, D., and Hammarskjold, M.-L. (1997) A structured retroviral RNA element that mediates nucleocytoplasmic export of introncontaining RNA. Mol. Cell. Biol. 17,135–144.PubMedGoogle Scholar
  76. 76.
    Mautino, M. R., Keiser, N., and Morgan, R. A. (2000) Improved titers of HIV based lentiviral vectors using the SRV-1 constitutive transport element. Gene Ther. 7, 1421–1424.PubMedCrossRefGoogle Scholar
  77. 77.
    Zufferey, R., Donello, J. E., Trono, D., and Hope, T. J. (1999) Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J. Virol. 73,2886–2892.PubMedGoogle Scholar
  78. 78.
    Ramezani, A., Hawley, T. S., and Hawley, R. G. (2000) Lentiviral vectors for enhanced gene expression in human hematopoietic cells. Mol. Ther. 2,458–469.PubMedCrossRefGoogle Scholar
  79. 79.
    Dunbar, C. E. and Emmons, R. V. B. (1994) Gene transfer into hematopoietic progenitor and stem cells: progress and problems. Stem Cells 12, 563–576.PubMedCrossRefGoogle Scholar
  80. 80.
    Stewart, A. K., Dubé, I. D., and Hawley, R. G. (1999) Gene marking and the biology of hematopoietic cell transfer in human clinical trials, in Blood Cell Biochemistry, Vol. 8: Hematopoiesis and Gene Therapy (Fairbairn, L. J. and Testa, N., eds.), Kluwer Academic/Plenum, New York, pp. 243–268.Google Scholar
  81. 81.
    Sorrentino, B. P. and Nienhuis, A. W. (1999) The hematopoietic system as a target for gene therapy, in The Development of Human Gene Therapy (Friedmann, T., ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 351–426.Google Scholar
  82. 82.
    Engel, B. C. and Kohn, D. B. (1999) Stem cell directed gene therapy. Frontiers Biosci. 4, e26–e33.CrossRefGoogle Scholar
  83. 83.
    Cavazzana-Calvo, M., Hacein-Bey, S., de Saint Basile, G., Gross, F., Yvon, E., Nusbaum, P., et al. (2000) Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288, 669–672.PubMedCrossRefGoogle Scholar
  84. 84.
    Cheshier, S. H., Morrison, S. J., Liao, X., and Weissman, I. L. (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc. Natl. Acad. Sci. USA 96, 3120–3125.PubMedCrossRefGoogle Scholar
  85. 85.
    Gothot, A., van der Loo, J. C. M., Clapp, D. W., and Srour, E. F. (1998) Cell cycle-related changes in repopulating capacity of human mobilized peripheral blood CD34+cells in non-obese diabetic/severe combined immune-deficient mice. Blood 92, 2641–2649.PubMedGoogle Scholar
  86. 86.
    Akkina, R. K., Walton, R. M., Chen, M. L., Li, Q.-X., Planelles, V., and Chen, I. S. Y. (1996) High-efficiency gene transfer into CD34+cells with a human immunodeficiency virus type 1-based retroviral vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G. J. Virol. 70,2581–2585.PubMedGoogle Scholar
  87. 87.
    Reiser, J., Harmison, G., Kluepfel-Stahl, S., Brady, R. O., Karlsson, S., and Schubert, M. (1996) Transduction of nondividing cells using pseudotyped defective high-titer HIV type 1 particles. Proc. Natl. Acad. Sci. USA 93,15,266–15,271.PubMedCrossRefGoogle Scholar
  88. 88.
    Uchida, N., Sutton, R. E., Friera, A. M., He, D., Reitsman, M. J., Chang, W. C., et al. (1998) HIV, but not murine leukemia virus, vectors mediate high efficiency gene transfer into freshly isolated G0/G1 human hematopoietic stem cells. Proc. Natl. Acad. Sci. USA 95,11,939–11,944.PubMedCrossRefGoogle Scholar
  89. 89.
    Case, S. S., Price, M. A., Jordan, C. T., Yu, X. J., Wang, L., Bauer, G., et al. (1999) Stable transduction of quiescent CD34(+)CD38(-) human hematopoietic cells by HIV-1-based lentiviral vectors. Proc. Natl. Acad. Sci. USA 96, 2988–2993.PubMedCrossRefGoogle Scholar
  90. 90.
    Sutton, R. E., Reitsma, M. J., Uchida, N., and Brown, R O. (1999) Transduction of human progenitor hematopoietic stem cells by human immunodeficiency virus type 1-based vectors is cell cycle dependent. J. Virol. 73, 3649–3660.PubMedGoogle Scholar
  91. 91.
    Salmon, P., Kindler, V., Ducrey, O., Chapuis, B., Zubler, R. H., and Trono, D. (2000) High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood 96, 3392–3398.PubMedGoogle Scholar
  92. 92.
    Miyoshi, H., Smith, K. A., Mosier, D. E., Verma, I. M., and Torbett, B. E. (1999) Transduction of human CD34+cells that mediate long-term engraftment of NOD/SCID mice by HIV-1 vectors. Science 283, 682–686.PubMedCrossRefGoogle Scholar
  93. 93.
    Guenechea, G., Gan, O.I., Inamitsu, T., Dorrell, C., Pereira, D. S., Kelly, M., et al. (2000) Transduction of human CD34+CD38- bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors. Mol. Ther. 1, 566–573.PubMedCrossRefGoogle Scholar
  94. 94.
    Woods, N.-B., Fahlman, C., Mikkola, H., Hamaguchi, I., Olsson, K., Zufferey, R., et al. (2000) Lentiviral gene transfer into primary and secondary NOD/SCID repopulating cells. Blood 96, 3725–3733.PubMedGoogle Scholar
  95. 95.
    Gao, Z., Golob, J., Tanavde, V. M., Civin, C. I., Hawley, R. G., and Cheng, L. (2001) High levels of transgene expression following transduction of long-term NOD/SCID-repopulating human cells with a modified lentiviral vector. Stem Cells 19,247–259.PubMedCrossRefGoogle Scholar
  96. 96.
    Sirven, A., Ravet, E., Charneau, P., Zennou, V., Coulombel, L., Guétard, D., et al. (2001) Enhanced transgene expression in cord blood CD34+-derived hematopoietic cells, including developing T cells and NOD/SCID mouse repopulating cells, following transduction with modified TRIP lentiviral vectors. Mol. Ther. 3,438–448.PubMedCrossRefGoogle Scholar
  97. 97.
    Woods, N.-B., Mikkola, H., Nilsson, E., Olsson, K., Trono, D., and Karlsson, S. (2001) Lentiviral-mediated gene transfer into hematopoietic stem cells. J. Intern. Med. 249, 339–343.PubMedCrossRefGoogle Scholar
  98. 98.
    Boshart, M., Weber, F., Jahn, G., Dorsch-Hasler, K., Fleckenstein, B., and Schaffner, W. (1985) A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell 41, 521–530.PubMedCrossRefGoogle Scholar
  99. 99.
    Baskar, J. F., Smith, P. P., Nilaver, G., Jupp, R. A., Hoffmann, S., Peffer, N. J., et al. (1996) The enhancer domain of the human major immediate-early promoter determines cell type-specific expression in transgenic mice. J. Virol. 70, 3207–3214.PubMedGoogle Scholar
  100. 100.
    An, D. S., Wersto, R. P., Agricola, B. A., Metzger, M. E., Lu, S., Amado, R. G., et al. (2000) Marking and gene expression by a lentivirus vector in transplanted human and nonhuman primate CD34+cells. J. Virol. 74, 1286–1295.PubMedCrossRefGoogle Scholar
  101. 101.
    Scharfmann, R., Axelrod, J. H., and Verma, I. M. (1991) Long-term in vivo expression of retrovirus-mediated gene transfer in mouse fibroblast implants. Proc. Natl. Acad. Sci. USA 88, 4626–4630.PubMedCrossRefGoogle Scholar
  102. 102.
    Kay, M. A., Baley, P., Rothenberg, S., Leland, F., Fleming, L., Ponder, K. P., et al. (1992) Expression of human α1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. Proc. Natl. Acad. Sci. USA 89, 89–93.PubMedCrossRefGoogle Scholar
  103. 103.
    Hawley, R. G., Lieu, F. H. L., Fong, A. Z. C., and Hawley, T. S. (1994) Versatile retroviral vectors for potential use in gene therapy. Gene Ther. 1, 136–138.PubMedGoogle Scholar
  104. 104.
    Eglitis, M. A., Schneiderman, R. D., Rice, P. M., and Eiden, M. V. (1995) Evaluation of retroviral vectors based on the gibbon ape leukemia virus. Gene Ther. 2, 486–492.PubMedGoogle Scholar
  105. 105.
    Kim, D. W., Uetsuki, T., Kaziro, Y., Yamaguchi, N., and Sugano, S. (1990) Use of the human elongation factor 1α promoter as a versatile and efficient expression system. Gene 91, 217–223.PubMedCrossRefGoogle Scholar
  106. 106.
    Niwa, H., Yamamura, K., and Miyazaki, J. (1991) Efficient selection for highexpression transfectants with a novel eukaryotic vector. Gene 108, 193–199.PubMedCrossRefGoogle Scholar
  107. 107.
    Lim, B., Apperley, J. F., Orkin, S. H., and Williams, D. A. (1989) Long-term expression of human adenosine deaminase in mice transplanted with retrovirusinfected hematopoietic stem cells. Proc. Natl. Acad. Sci. USA 86, 8892–8896.PubMedCrossRefGoogle Scholar
  108. 108.
    Rivella, S. and Sadelain, M. (1998) Genetic treatment of severe hemoglobinopathies: the combat against transgene variegation and transgene silencing. Semin. Hematol. 35, 112–125.PubMedGoogle Scholar
  109. 109.
    Emery, D. W. and Stamatoyannopoulos, G. (1999) Stem cell gene therapy for the β-chain hemoglobinopathies. Problems and progress. Ann. N.Y. Acad. Sci. 872, 94–107.PubMedCrossRefGoogle Scholar
  110. 110.
    Gasser, S. M. (2001) Positions of potential: nuclear organization and gene expression. Cell 104, 639–642.PubMedCrossRefGoogle Scholar
  111. 111.
    Hawley, R. G. (2001) Progress toward vector design for hematopoietic stem cell gene therapy. Curr. Gene Ther. 1,1–17.PubMedCrossRefGoogle Scholar
  112. 112.
    Hawley, T. S., Sabourin, L. A., and Hawley, R. G. (1989) Comparative analysis of retroviral vector expression in mouse embryonal carcinoma cells. Plasmid 22, 120–131.PubMedCrossRefGoogle Scholar
  113. 113.
    Rasheed, S., Nelson-Rees, W.A., Toth, E. M., Arnestein, P., and Gardner, M. B. (1974) Characterization of a newly derived human sarcoma cell line (HT-1080). Cancer 33,1027–1033.PubMedCrossRefGoogle Scholar
  114. 114.
    Moritz, T., Patel, V. P., and Williams, D. A. (1994) Bone marrow extracellular matrix molecules improve gene transfer into human hematopoietic cells via retroviral vectors. J. Clin. Invest. 93, 1451–1457.PubMedCrossRefGoogle Scholar
  115. 115.
    Donahue, R. E., Sorrentino, B. P., Hawley, R. G., An, D. S., Chen, I. S. Y., and Wersto, R. P. (2001) Fibronectin fragment CH-296 inhibits apoptosis and enhances ex vivo gene transfer by murine retrovirus and human lentivirus vectors independent of viral tropism in non-human primate CD34+cells. Mol. Ther. 3, 359–367.PubMedCrossRefGoogle Scholar
  116. 116.
    Bahnson, A. B., Dunigan, J. T., Baysal, B. E., Mohney, T., Atchison, R. W., Nimgaonkar, M. T., et al. (1995) Centrifugal enhancement of retroviral mediated gene transfer. J. Virol. Meth. 54, 131–143.CrossRefGoogle Scholar
  117. 117.
    Gervaix, A., West, D., Leoni, L. M., Richman, D. D., Wong-Staal, F., and Corbeil, J. (1997) A new reporter cell line to monitor HIV-1 infection and drug susceptibility in vitro. Proc. Natl. Acad. Sci. USA 94, 4653–4658.PubMedCrossRefGoogle Scholar
  118. 118.
    Higashikawa, F. and Chang, L.-J. (2001) Kinetic analyses of stability of simple and complex retroviral vectors. Virology 280, 124–131.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Ali Ramezani
    • 1
  • Robert G. Hawley
    • 2
    • 3
  1. 1.Department of Hematopoiesis, Jerome H. Holland Laboratory for the Biomedical SciencesAmerican Red CrossRockville
  2. 2.Cell Therapy Research and Development, Jerome H. Holland Laboratory for the Biomedical SciencesAmerican Red CrossRockville
  3. 3.Department of Anatomy and Cell BiologyThe George Washington University Medical CenterWashington

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