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Gene Therapy

  • Richard A. Morgan

Abstract

Therapeutic strategies for intervening in HIV disease currently include antiretroviral therapy, treatment and prophylaxis of opportunistic infections, antitumor therapy, immuno-modulator therapy, and immunologic restoration using the immune-based therapies described in this book. There are, however, some significant practical and theoretical difficulties with available antiretroviral agents. Although mortality and frequency of opportunistic infections are reduced in patients taking zidovudine, a complete and sustained improvement in immune status has not been achieved (Fischl et al., 1989). In addition, frequent toxic effects prevent many individuals from tolerating these drugs for extended periods (Richman et al., 1987). Recent in vitro evidence of retroviral resistance has also been presented, although the clinical importance of this is as yet unknown (Larder et al., 1989). In hopes of increasing efficacy and reducing toxicity, studies are now under way examining the potential role of combination therapies for HIV infection (Fauci, 1992). Such approaches include combined therapy with two or more agents from the same class [e. g., reverse transcriptase (RT) inhibitors] or from distinct classes with different mechanisms of action (e. g., RT inhibitors plus immunomodulators). Despite the major advances in treating HIV disease that have occurred in the past 5 years, it is clear that the need is still great for more efficacious, less toxic therapies with novel mechanisms of action. It is therefore important to explore and develop new modalities for the treatment of this deadly disease. Gene therapy, defined as the introduction of new genetic material into cells of an individual with resulting therapeutic benefit to the individual, may be an effective treatment for a variety of disorders (Anderson, 1984; Morgan and Anderson, 1993). Since HIV integrates itself into the host’s genome, AIDS can be considered an “acquired genetic disease” and thus potentially amenable to treatment using gene therapy.

Keywords

Human Immunodeficiency Virus Gene Therapy Human Immunodeficiency Virus Type Human Immunodeficiency Virus Infection Human Immunodeficiency Virus Replication 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adam, M. A., and Miller, A. D., 1988, Identification of a signal in a murine retrovirus that is sufficient for packaging of nonretroviral RNA into virions, J. Virol. 62:3802–3806.PubMedGoogle Scholar
  2. Alexander, I. E., Russell, D. W., and Miller, A. D., 1994, DNA-damaging agents greatly increase the transduction of nondividing cells by adeno-associated virus vectors, J. Virol. 68:8282–8287.PubMedGoogle Scholar
  3. Anderson, W. F., 1984, Prospects toward human gene therapy, Science 226:401–409.PubMedCrossRefGoogle Scholar
  4. Apperly, J. F., Luskey, B. D., and Williams, D. A., 1991, Retroviral gene transfer of human adenosine deaminase in murine hematopoietic cells: Effect of selectable marker sequences on long-term expression, Blood 78:310–317.Google Scholar
  5. Armentano, D., Yu, S. K., Kantoff, P. W., von Ruden, T., Anderson, W. F., and Gilboa, E., 1987, Effects of internal viral sequences on the utility of recombinant retroviral vectors, J. Virol. 61:1647.PubMedGoogle Scholar
  6. Bahner, I., Zhou, C., Yu, X. J., Guatelli, J. C., and Kohn, D. B., 1993, Comparison of trans-dominant inhibitory mutant human immunodeficiency virus type 1 genes expressed by retroviral vectors in human T lymphocytes, J. Virol. 67:3199–3207.PubMedGoogle Scholar
  7. Banda, N. K., Bernier, J., Kurahara, D. K., Kurrle, R., Haigwood, N., Sekaly, R. P., and Finkel, T. H., 1992, Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis, J. Exp. Med. 176:1099–1106.PubMedCrossRefGoogle Scholar
  8. Blaese, R. M., Culver, K. W., Miller, A. D., Carter, C. S., Fleisher, T., Clerici, M., Shearer, G., Chang, L., Chiang, Y., Tolstoshev, P., Greenblatt, J. J., Rosenberg, S. A., Klein, H., Berger, M., Mullen, C. A., Ramsey, W. J., Muul, L., Morgan, R. A., and Anderson, W. F., 1995, T lymphocyte directed gene therapy for ADA deficiency (SCID): Results of the initial trial with 4 years of observation, Science 270:475–480.PubMedCrossRefGoogle Scholar
  9. Bunnell, B. A., Muul, L. M., Donahue, R. E., Blaese, R. M., and Morgan, R. A., 1995, High-efficiency retroviral-mediated gene transfer into human and nonhuman primate peripheral blood lymphocytes, Proc. Natl. Acad. Sci. USA 92:7739–7743.PubMedCrossRefGoogle Scholar
  10. 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 non-mammalian cells, Proc. Natl. Acad. Sci. USA 90:8033–8037.PubMedCrossRefGoogle Scholar
  11. Carmichael, A., Jin, X., Sissons, P., and Borysiewicz, L., 1993, Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: Differential CTL responses to HTV-1 and Epstein-Barr virus in late disease, J. Exp. Med. 177:249–256.PubMedCrossRefGoogle Scholar
  12. Challita, P.-M., and Kohn, D. B., 1994, Lack of expression from a retroviral vector after transduction of murine hematopoietic stem cells is associated with methylation in vivo, Proc. Natl. Acad. Sci. USA 91:2567–2571.PubMedCrossRefGoogle Scholar
  13. Chen, C. J., Banerjea, A. C., Hamison, G. G., Hagland, K., and Schubert, M., 1992, Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication-potential effectiveness against most presently sequenced HIV-1 isolates, Nucleic Acids Res. 20:4581–4589.PubMedCrossRefGoogle Scholar
  14. Chuah, M. K. L., VandenDriessche, T., Chang, H., Ensoli, B., and Morgan, R. A., 1994, Inhibition of human immunodeficiency virus type-1 by retroviral vectors expressing antisense TAR, Hum. Gene Then 5:1467–1475.CrossRefGoogle Scholar
  15. Culver, K. C., Morgan, R. A., Osborne, W. R. A., Lee, T., Lenscow, D., Able, C., Cornetta, K., Anderson, W. R., and Blaese, R. M., 1990, In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys, Hum. Gene Ther. 1:399–409.PubMedCrossRefGoogle Scholar
  16. Danos, O., and Mulligan, R. C., 1988, Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges, Proc. Natl. Acad. Sci. USA 85:6460–6464.PubMedCrossRefGoogle Scholar
  17. Duan, L., Bagasra, O., Laughlin, M. A., Oakes, J. W., and Pomerantz, R. J., 1994, Potent inhibition of human immunodeficiency virus type 1 by an intracellular anti-Rev single-chain antibody, Proc. Natl. Acad. Sci. USA 91:5075–5079.PubMedCrossRefGoogle Scholar
  18. Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R. C., and Wong-Staal, F., 1990, Tat protein of HIV-1 stimulates growth of cells derived from Kaposi’s sarcoma lesions of AIDS patients, Nature 344:84–86.CrossRefGoogle Scholar
  19. Esaich, S., Kalfoglou, C., Plavec, I., Kaushal, S., Mosca, J. D., and Bohnlein, E., 1995, RevM10-mediated inhibition of HIV-1 replication in chronically infected T-cells, Hum. Gene Ther. 6:625–634.CrossRefGoogle Scholar
  20. Fauci, A. S., 1992, Combination therapy for HIV infection: Getting closer, Ann. Intern. Med. 116:85–86.PubMedCrossRefGoogle Scholar
  21. Fauci, A. S., Schnittman, S. M., Poli, G., Koenig, S., and Pantaleo, G., 1991, Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection, Ann. Intern. Med. 114:678–693.PubMedCrossRefGoogle Scholar
  22. Feinberg, M. B., and Trono, D., 1992, Intracellular immunization: Trans-dominant mutants of HIV gene products as tools for the study and interruption of viral replication, AIDS Res. Hum. Retrovir. 8:1013–1022.PubMedCrossRefGoogle Scholar
  23. Feigner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., Ringold, G. M., and Danielsen, M., 1987, Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure, Proc. Natl. Acad. Sci. USA 84:7413–7417.CrossRefGoogle Scholar
  24. Fischl, M. A., Richman, D. D., Causey, D. M., Grieco, M. H., Bryson, Y., Mildvan, D., Laskin, O. L., Groopman, J. E., Volberding, P. A., Schooley, R. T., Jackson, G. G., Durack, D. T., Andrews, J. C., Nusinoff-Lehrman, S., Barry, D. W., and the AZT Collaborative Working Group, 1989, Prolonged zidovudine therapy in patients with AIDS and advanced AIDS-related complex. AZT Collaborative Working Group, J. Am. Med. Assoc. 262:2405–2410.CrossRefGoogle Scholar
  25. Gilboa, E., and Smith, C., 1994, Gene therapy for infectious diseases: The AIDS Model, Trends Genet. 10:139–144.PubMedCrossRefGoogle Scholar
  26. Halbert, C. L., Alexander, I. E., Wolgamot, G. M., and Miller, A. D., 1995, Adeno-associated virus vectors transduce primary cells much less efficiently than immortalized cells, J. Virol. 69:1473–1479.PubMedGoogle Scholar
  27. Herskowitz, I., 1987, Functional inactivation of genes by dominant negative mutations, Nature 329:219–222.PubMedCrossRefGoogle Scholar
  28. Jolly, D., Chada, S., Townsend, K., De Jesus, C., Chang, S., Weinhold, K., Anderson, C.-G., Lynn, A., Bodner, M., Barber, J., and Warner, J., 1992, CTL cross reactivity between HIV strains, AIDS Res. Hum. Retrovir. 8:1369–1371.PubMedGoogle Scholar
  29. Jowett, J. B., Planelles, V., Poon, B., Shah, N. P., Chen, M. L., and Chen, I. S. Y., 1995, The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2+ M phase of the cell cycle, J. Virol. 69:6304–6313.PubMedGoogle Scholar
  30. Kinchington, D., Galpin, S., Jaroszewski, J., Ghosh, K., Sabasinghe, C., and Cohen, J. S., 1992, A comparison of gag, pol and rev antisense oligodeoxynucleotides as inhibitors of HIV-1, Antiviral Res. 17:53–62.PubMedCrossRefGoogle Scholar
  31. Kohn, D., B., Weinberg, K. I., Parkman, R., Lenarsky, C., Crooks, G. M., Shaw, K., Hanley, M. E., Lawrence, K., Annett, G., Brooks, J. S., Wara, D., Elder, M., Bowen, T., Hershfield, M. S., Berenson, R. I., Moen, R. C., Mullen, C. A., and Blaese, R. M., 1994, Gene therapy for neonates with ADA-deficient SCID by retroviral-mediated transfer of the human ADA cDNA into umbilical cord CD34+ cells, J. Cell. Biochem. Suppl. 18A:238.Google Scholar
  32. Larder, B. A., Darby, G., and Richman, D. D., 1989, HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy, Science 243:1731–1734.PubMedCrossRefGoogle Scholar
  33. Leavitt, M. C., Yu, M., Yamada, O., Kraus, G., Looney, D., Poeschla, E., and Wong-Staal, F., 1994, Transfer of an anti-HIV-1 ribozyme gene into primary human lymphocytes, Hum. Gene Then 5:1115–1120.CrossRefGoogle Scholar
  34. Ledley, F. D., 1995, Nonviral Gene Therapy: The promise of genes as pharmaceutical products, Hum. Gene Then 6:1129–1144.CrossRefGoogle Scholar
  35. Lee, S. W., Gallardo, H. F., Gilboa, E., and Smith, C., 1994, Inhibition of human immunodeficiency virus type 1 in human T cells by a potent Rev response element decoy consisting of the 13-nucleotide minimal Rev-binding domain, J. Virol. 68:8254–8264.PubMedGoogle Scholar
  36. Lin, H., Parmacek, M. S., Marie, G., Boiling, S., and Leiden, J. M., 1990, Expression of recombinant genes in myocardium in vivo after direct injection of DNA, Circulation 82:2217–2221.PubMedCrossRefGoogle Scholar
  37. Lisziewicz, J., Sun, D., Smythe, J., Lusso, P., Loni, F., Louie, A., Markham, P., Rossi, J., Reitz, M., and Gallo, R. C., 1993, Inhibition of human immunodeficiency virus type 1 replication by regulated expression of a polymeric Tat activation response RNA decoy as a strategy for gene therapy for AIDS, Proc. Natl. Acad. Sci. USA 90:8000–8004.PubMedCrossRefGoogle Scholar
  38. Lu, S., Santoro, J. S., Fuller, D. H., Hayes, J. R., and Robinson, H. L., 1995, Use of DNAs expressing HIV-1 env and noninfectious HIV-1 particles to raise antibody-responses in mice, Virology 209:147–154.PubMedCrossRefGoogle Scholar
  39. Malim, M. H., Bohnlein, S., Hauber, J., and Cullen, B. R., 1989, Functional dissection of the HIV-1 Rev trans-activator: Derivation of a transdominant repressor of rev function, Cell 58:205–214.PubMedCrossRefGoogle Scholar
  40. Mann, R., Mulligan, R. C., and Baltimore, D., 1983, Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus, Cell 33:153–159.PubMedCrossRefGoogle Scholar
  41. Marasco, W. A., Haseltine, W. A., and Chen, S. Y., 1993, Design intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody, Proc. Natl. Acad. Sci. USA 90:7889–7893.PubMedCrossRefGoogle Scholar
  42. Markowitz, D., Goff, S., and Bank, A., 1988, A safe packaging cell line for gene transfer: Separating viral genes on two different plasmids, J. Virol. 62:1120–1124.PubMedGoogle Scholar
  43. Mhashilkar, A. M., Bagley, J., Chen, S. Y., Szilvoy, A. M., Heiland, D. G., and Marasco, W. A., 1995, Inhibition of HIV-1 Tat-mediated LTR transactivation and HIV-1 infection by anti-Tat single chain intrabodies, EMBO J. 14:1542–1551.PubMedGoogle Scholar
  44. Miller, A. D., 1992, Retroviral vectors, Curr. Top Microbiol. Immunol. 158:1–24.PubMedCrossRefGoogle Scholar
  45. 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.PubMedGoogle Scholar
  46. Miller, A. D., Garcia, J. V., von Suhr, N., Lynch, M., Wilson, C., and Eden, M. V., 1991, Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus, J. Virol. 65:2220–2224.PubMedGoogle Scholar
  47. Morgan, R. A., 1994, Retroviral vectors in human gene therapy, in: Human Viruses in Gene Therapy (J.-M. H. Vos, ed.), Academic Pres, San Diego, pp. 77–107.Google Scholar
  48. Morgan, R. A., and Anderson, W. F., 1993, Human gene therapy, Annu. Rev. Biochem. 62:191–217.PubMedCrossRefGoogle Scholar
  49. Morvan, F., Porumb, H., Degols, G., Lefebvre, I., Pompon, A., Sproat, B. S., Rayner, B., McIvy, C., Lebl, B., and Imbach, J. L., 1993, Comparative evaluation of seven oligonucleotide analogues as potential antisense agents, J. Med. Chem. 36:280–287.PubMedCrossRefGoogle Scholar
  50. Mulligan, R. C., 1993, The basic science of gene therapy, Science 260:926–932.PubMedCrossRefGoogle Scholar
  51. Muzyczka, N., 1992, Use of adeno-associated virus as a general transduction vector for mammalian cells, Curr. Top. Microbiol. Immunol. 158:97–129.PubMedCrossRefGoogle Scholar
  52. Nabel, E. G., Gordon, D., Yang, Z.-Y., Xu, L., San, H., Plautz, G. E., Wu, B. Y., Gao, K., Huang, L., and Nabel, G. J., 1992, Gene transfer in vivo with DNA-liposome complexes: Lack of autoimmunity and gonadal localization, Hum. Gene. Then 3:649–656.CrossRefGoogle Scholar
  53. Pantaleo, G., Koenig, S., Baseler, M., Lane, H. C., and Fauci, A. S., 1990, Defective clonogenic potential of CD8+ lymphocytes in patients with AIDS: Expansion in vivo of a nonclonogenic CD3+ CD8+ DR+ CD25 — T cell population, J. Immunol. 144:1696–1704.PubMedGoogle Scholar
  54. Ragheb, J. A., Bressler, P., Daucher, M., Chiang, L., Chuah, M. K. L., VandenDriessche, T., and Morgan, R. A., 1996, Analysis of transdominant mutants of the HIV-1 rev protein for their ability to inhibit Rev function, HIV-1 replication, and their use as anti-HIV gene therapeutics, AIDS Res. Hum. Retrovir. 11:1343–1353.CrossRefGoogle Scholar
  55. Reusser, P., Riddell, S. R., Meyers, J. D., and Greenberg, P. D., 1991, Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: Pattern of recovery and correlation with cytomegalovirus infection and disease, Blood 78:1373–1380.PubMedGoogle Scholar
  56. Richman, D. D., Fischl, M. A., Grieco, M. H., Gottlieb, M. S., Volberding, P. A., Laskin, O. L., Leedom, J. M., Groopman, J. E., Mildvan, D., Hirsch, M. S., Jackson, G. G., Durack, D. T., Nusinoff-Lehrman, S., and the AZT Collaborative WorkingGroup, 1987, The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: A double-blind, placebo-controlled trial, N. Engl. J. Med. 317:192–197.PubMedCrossRefGoogle Scholar
  57. Riddell, S. R., Greenberg, P. D., Overell, R. W., Loughran, T. P., Gilbert, M. J., Lupton, S. O., Agosti, J., Scheeler, S., Coombs, R. W., and Corey, L., 1992, Phase I study of cellular adoptive immunotherapy using genetically modified CD8+ HIV-specific T-cells for HIV seropositive patients undergoing allogeneic bone marrow transplant, Hum. Gene Ther. 3:319–338.PubMedCrossRefGoogle Scholar
  58. Riddell, S. R., Elliott, M., Lewinsohn, D. A., Gilbert, M. J., Wilson, L., Manley, S. A., Lupton, S. D., Overell, R. W., Reynolds, T. C., Corey, L., and Greenberg, P. D., 1996, T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients, Nature Medicine 2:216–223.PubMedCrossRefGoogle Scholar
  59. Rill, D. R., Moen, R. C., Buschle, M., Bartholomew, C., Foreman, N. K., Mirro, J., Jr., Krance, R. A., Ihle, J. N., and Brenner, M. K., 1992, An approach for the analysis of relapse and marrow reconstitution after autologous marrow transplantation using retrovirus-mediated gene transfer, Blood 79:2694–2700.PubMedGoogle Scholar
  60. Rosenberg, S. A., Aebersold, P. M., Cornetta, K., Kasid, A., Morgan, R. A., Moen, R., Karson, E. M., Lotze, M. T., Yang, J. C., Topalien, S. L., Merino, M. J., Culver, K., Miller, A. D., Blaese, R. M., and Anderson, W. F., 1990, Gene transfer into humans: Immunotherapy of patients with advanced melanoma using tumor infiltrating lymphocytes modified by retroviral gene transduction, N. Engl. J. Med. 323:570–578.PubMedCrossRefGoogle Scholar
  61. Samulski, R. J., 1994, Parvoviruses, in: Human Viruses in Gene Therapy (J.-M. H. Vos, ed.), Academic Press, San Diego, pp. 53–76.Google Scholar
  62. Sarver, N., Cantin, E. M., Chang, P. S., Zaia, J. A., Ladne, P. A., Stephens, D. A., and Rossi, J. J., 1990, Ribozymes as potential anti-HIV-1 therapeutic agents, Science 247:1222–1225.PubMedCrossRefGoogle Scholar
  63. Stewart, M. J., Plautz, G. E., Yang, Z.-Y, Xu, L., Gao, X., Huang, L., Nabel, E. G., and Nabel, G. J., 1992, Gene transfer in vivo with DNA-liposome complexes: Safety and acute toxicity in mice, Hum. Gene. Ther. 3:267–275.PubMedCrossRefGoogle Scholar
  64. Sullenger, B. A., Gallardo, H. R., Ungers, G. E., and Gilboa, E., 1991, Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation, J. Virol. 65:6811–6816.PubMedGoogle Scholar
  65. Van Beusechem, V. W., Kukler, A., Heidt, P. J., and Valerio, D., 1992, Long-term expression of human adenosine deaminase in rhesus monkeys transplanted with retrovirus-infected bone-marrow cells, Proc. Natl. Acad. Sci. USA 89:7640–7644.PubMedCrossRefGoogle Scholar
  66. VandenDriessche, T., Chuah, M. K. L., and Morgan, R. A., 1994, Gene therapy for acquired immune deficiency syndrome, in: AIDS Updates Volume 7(4) (V. T. DeVita, S. Hellman, and S. A. Rosenberg, eds.), Lippincott, Philadelphia, pp. 1–14.Google Scholar
  67. VandenDriessche, T., Chuah, M. K. L., Chiang, L., Chang, H. K., Ensoli, B., and Morgan, R. A., 1995, Inhibition of clinical HIV-1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes, J. Virol. 69:4045–4052.PubMedGoogle Scholar
  68. Walker, B. D., and Plata, F., 1990, Cytotoxic T lymphocytes against HIV, AIDS 4:177–184.PubMedCrossRefGoogle Scholar
  69. Walker, R., 1993, A study of the safety and survival of the adoptive transfer of genetically marked syngeneic lymphocytes in HIV-infected identical twins, Hum. Gene Ther. 4:659–680.PubMedCrossRefGoogle Scholar
  70. Warner, J. F., Anderson, C.-G., Laube, I., Jolly, D. J., Townsend, K., Chada, S., and St. Louis, D., 1991, Induction of HIV-specific CTL and antibody responses in mice using retroviral vector-transduced cells, AIDS Res. Hum. Retrovir. 7:645–655.PubMedCrossRefGoogle Scholar
  71. Woffendin, G., Yang, Z.-Y, Udaykumar, Xu, L., Yang, N. S., Sheehy, M. J., and Nabel, G. J., 1994, Nonviral and viral delivery of a human immunodeficiency virus protective gene into primary human T cells, Proc. Natl. Acad. Sci. USA 91:11581–11585.PubMedCrossRefGoogle Scholar
  72. Wong-Staal, F., Yu, M., Yamada, O., et al., 1994, Development of ribozyme gene therapy against HIV, J. Cell Biochem. Suppl. 18A:221.Google Scholar
  73. Yang, Y., Vanin, E. F., Whitt, M. A., Fornerod, M., Zwart, R., Schneiderman, R. D., Grosveld, G., and Nienhuis, A. W., 1995, Inducible high-level production of infectious murine leukemia retroviral vector particles psuedotyped with vesicular stomatitis virus G envelope protein, Hum. Gene Ther. 6:1203–1213.PubMedCrossRefGoogle Scholar
  74. Yu, M. Poeschla, E., and Wong-Staal, F., 1994, Progress towards gene therapy for HIV infection, Gene Then 1:13–26.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Richard A. Morgan
    • 1
  1. 1.Clinical Gene Therapy BranchNational Center for Human Genome Research, National Institutes of HealthBethesdaUSA

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