Skip to main content
Log in

Viral Vectors for Gene Transfer

A Review of Their Use in the Treatment of Human Diseases

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

The efficient delivery of therapeutic genes and appropriate gene expression are the crucial issues for clinically relevant gene therapy. Viruses are naturally evolved vehicles which efficiently transfer their genes into host cells. This ability made them desirable for engineering virus vector systems for the delivery of therapeutic genes. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Among these vector systems, retrovirus vectors represent the most prominent delivery system, since these vectors have high gene transfer efficiency and mediate high expression of therapeutic genes. Members of the DNA virus family such as adenovirus-, adeno-associated virus or herpes-virus have also become attractive for efficient gene delivery as reflected by the fast growing number of clinical trials using these vectors.

The first clinical trials were designed to test the feasibility and safety of viral vectors. Numerous viral vector systems have been developed for ex vivo and in vivo applications. More recently, increasing efforts have been made to improve infectivity, viral targeting, cell type specific expression and the duration of expression. These features are essential for higher efficacy and safety of RNA- and DNA-virus vectors. From the beginning of development and utilisation of viral vectors it was apparent that they harbour risks such as toxicities, immunoresponses towards viral antigens or potential viral recombination, which limit their clinical use. However, many achievements have been made in vector safety, the retargeting of virus vectors and improving the expression properties by refining vector design and virus production.

This review addresses important issues of the current status of viral vector design and discusses their key features as delivery systems in gene therapy of human inherited and acquired diseases at the level of laboratory developments and of clinical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Blease RM, Culver KW, Anderson WE. The ADA human gene therapy clinical protocol. Hum Gene Ther 1990; 1: 331–7

    Article  Google Scholar 

  2. Rosenberg SA, Aebersold P, Cornetta K, et al. Gene transfer into humans: immunotherapy of patients with advanced melanoma, using tumour infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 1990; 323: 570–8

    Article  PubMed  CAS  Google Scholar 

  3. Miller DG, Adam MA, Miller AD. Gene transfer by retrovirus vector occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 1990; 10: 4139–42

    Google Scholar 

  4. Gilboa E, Eglitis MA, Kantoff PW, et al. Transfer and expression of cloned genes using retroviral vectors. Biotechniques 1986; 4: 504–12

    CAS  Google Scholar 

  5. Guild BC, Finer MF, Housman DE, et al. Develoment of retroviral vectors useful for expressing genes in cultured embryonal cells and hematopoietic cells in vivo. J Virol 1988; 62: 3795–801

    PubMed  CAS  Google Scholar 

  6. Battini JL, Danos O, Heard JM. Receptor binding domain of murine leukaemia virus envelope glycoproteins. J Virol 1992; 66: 713–9

    Google Scholar 

  7. Miller DG, Miller AD. A family of retroviruses that utilise related phosphate transporters for cell entry. J Virol 1994; 68: 8270–6

    PubMed  CAS  Google Scholar 

  8. Markowitz D, Goff S, Bank A. A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol 1988; 62: 1120–4

    PubMed  CAS  Google Scholar 

  9. Dzierzak EA, Papayannopoulou T, Mulligan RC. Lineage specific expression of a human beta-globin gene in murine bone marrow transplant recipients reconstituted with retrovirus transduced stem cells. Nature 1988; 331: 35–41

    Article  PubMed  CAS  Google Scholar 

  10. Sadelain M, Wang CH, Antiniou M, et al. Generation of a high titre retroviral vector capable of expressing high levels of the human beta-globin gene. Proc Natl Acad Sci U S A 1995; 92: 6728–32

    Article  PubMed  CAS  Google Scholar 

  11. Ohashi T, Boggs S, Robbins P, et al. 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 U S A 1992; 89: 11332–6

    Article  PubMed  CAS  Google Scholar 

  12. Emerman M, Temin HM. Comparison of promoter suppression in avian and murine retrovirus vectors. Nucl Acids Res 1986; 14: 9381–96

    Article  PubMed  CAS  Google Scholar 

  13. Walther W, Stein U. Cell type specific and inducible promoters for vectors in gene therapy as an approach for cell targeting. J Mol Med 1996; 74: 379–92

    Article  PubMed  CAS  Google Scholar 

  14. Hantzopoulos PA, Sullenger BA, Ungers G, et al. Improved gene expression upon transfer of the adenosine deaminase minigene outside the transcriptional unit of the retroviral vector. Proc Natl Acad Sci U S A 1989; 86: 3519–23

    Article  PubMed  CAS  Google Scholar 

  15. Salmons B, Sailer RM, Baumann J, et al. Construction of retroviral vectors for targeted delivery and expression of therapeutic genes. Leukaemia 1995; 9 Suppl. 1: 53–60

    Google Scholar 

  16. Mrochen S, Klein D, Salmons B, et al. Inducible expression of p21WAF-1/CIP-1/SDI-1 from a promoter-conversion retroviral vector. J Mol Med 1997; 75: 820–8

    Article  PubMed  CAS  Google Scholar 

  17. Yu SF, von Ruden T, Kantoff PW, et al. Self-inactivating retroviral vectors designed for transfer of whole genes into mam-malian cells. Proc Natl Acad Sci U S A 1986; 83: 3194–8

    Article  PubMed  CAS  Google Scholar 

  18. Ghattas IR, Sanes JR, Majors JE. The encephalomyocarditis virus interna ribosomal entry site allows efficient coexpression of two genes from a recombinant provirus in cultured cells and embryos. Mol Cell Biol 1991; 11: 5848–59

    PubMed  CAS  Google Scholar 

  19. Morgan RA, Couture L, Elroy-Stein O, et al. Retroviral vectors containing putative internal ribosomal entry sites: development of a polycistronic gene transfer system and applications to human gene therapy. Nucl Acids Res 1992; 20: 1293–9

    Article  PubMed  CAS  Google Scholar 

  20. Chen BF, Hwang LH, Chen DS. Characterisation of a bicistronic vector composed of the swine vesicular disease virus internal ribosomal entry site. J Virol 1993; 67: 2142–8

    PubMed  CAS  Google Scholar 

  21. Wadhwa R, Smith-Pereira OM, Reddel RR, et al. Correlation between complementation group for immortality and the cellular distribution of mortalin. Exp Cell Res 1995; 216: 101–6

    Article  PubMed  CAS  Google Scholar 

  22. Zitvogel L, Tahara R, Mueller G, et al. Construction and characterisation of retroviral vectors expressing biologically actice human interleukin 12. Hum Gene Ther 1994; 5: 1493–506

    Article  PubMed  CAS  Google Scholar 

  23. Lund AH, Duch M, Pedersen FS. Transcriptional silencing of retroviral vectors. J Biomed Sci 1996; 3: 365–78

    Article  PubMed  CAS  Google Scholar 

  24. Richards CA, Huber BE. Generation of a transgenic model for retrovirus-mediated gene therapy of hepatocellular carcinoma is thwarted by the lack of transgene expression. Hum Gene Ther 1993; 4: 143–50

    Article  PubMed  CAS  Google Scholar 

  25. Vernet M, Cebrian J. cis-Acting elements that mediate the negative regulation of Moloney murine leukaemia virus in mouse early embryos. J Virol 1996; 70: 5630–3

    PubMed  CAS  Google Scholar 

  26. Challita PM, Skelton D, El-Khoueiry A, et al. Multiple modification in cis elements of the long terminal repeat of retroviral vectors lead to increase expression and decrease DNA methylation in embryonic carcinoma cells. J Virol 1995; 69: 748–55

    PubMed  CAS  Google Scholar 

  27. Wang H, Kavanough MP, North RA, et al. Cell surface receptor for ecotropic murine retroviruses is a basic amino acid transporter. Nature 1991; 352: 729–31

    Article  PubMed  CAS  Google Scholar 

  28. Young JAT, Bates P, Willert K, et al. Efficient incorporation of human CD4 protein into avian leukosis virus particles. Science 1990; 250: 1421–3

    Article  PubMed  CAS  Google Scholar 

  29. Russell SJ, Hawkins RE, Winter G. Retroviral vectors displaying functional antibody fragments. Nucleic Acids Res 1993; 21: 1081–5

    Article  PubMed  CAS  Google Scholar 

  30. Kasahara K, Dozy AM, Kann YW. Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. Science 1994; 266: 1373–6

    Article  PubMed  CAS  Google Scholar 

  31. Valsesia-Wittman S, Drynda A, Deleage G, et al. Modifications in the binding domain of avian retrovirus envelope protein to redirect the host range of retroviral vectors. J Virol 1994; 68: 4609–19

    Google Scholar 

  32. Han X, Kasahara N, Kann YW. Ligand-directed retroviral targeting of human breast cancer cells. Proc Natl Acad Sci U S A 1995; 92: 9747–51

    Article  PubMed  CAS  Google Scholar 

  33. Chu TH, Dornburg R. Toward highly efficient cell-type specific gene transfer with retroviral vectors displaying single-chain antibodies. J Virol 1997; 71: 720–5

    PubMed  CAS  Google Scholar 

  34. Yee J, Miyanohara A, Laporte P, et al. A general method for the generation of high-titer, pantropic retroviral vectors: Highly efficient infection of primary hepatocytes. Proc Natl Acad Sci U S A 1994; 91: 9564–8

    Article  PubMed  CAS  Google Scholar 

  35. Sharma S, Cantwell M, Kipps TJ, et al. Efficient infetion of a human T-cell line and of human primary peripheral blood leucocytes with a pseudotyped retrovirus vector. Proc Natl Acad Sci U S A 1996; 93: 11842–7

    Article  PubMed  CAS  Google Scholar 

  36. Sinclair AM, Agrawal YP, Elbar E, et al. Interaction of vesicular stomatitis virus-G pseudotyped retovirus with CD34+ and CD34-+CD38+ hematopoietic progenitors. Gene Ther 1997; 4: 918–27

    Article  PubMed  CAS  Google Scholar 

  37. Somia N, Zopp EM, Verma I. Generation of targeted retroviral vectors by using single-chain variable fragment: an approach to in vivo gene delivery. Proc Natl Acad Sci U S A 1995; 92: 7570–4

    Article  PubMed  CAS  Google Scholar 

  38. Marin M, Noël D, Valsesia-Wittman S, et al. Targeted infection of human cells via major histocompatibility complex class I molecules by moloney murine leukaemia virus-derived virus displaying single-chain antibody fragment-envelope proteins. J Virol 1996; 70: 2957–62

    PubMed  CAS  Google Scholar 

  39. Cosset FL, Morling FJ, Takeuchi Y, et al. Retroviral targeting by envelopes expressing an N terminal binding domain. J Virol 1995; 69: 6314–22

    PubMed  CAS  Google Scholar 

  40. Schnierle B, Groner B. Retroviral targeted delivery. Gene Ther 1996; 3: 1069–73

    PubMed  CAS  Google Scholar 

  41. Ager S, Nilson BHK, Morling FJ, et al. Retroviral display of antibody fragments; interdomain spacing strongly influences vector infectivity. Hum Gene Ther 1996; 7: 2157–64

    Article  PubMed  CAS  Google Scholar 

  42. Schnierle B, Moritz D, Jeschke M, et al. Expression of chimeric envelope proteins in helper cell lines and integration into Moloney murine leukaemia virus particles. Gene Ther 1996; 3: 334–42

    PubMed  CAS  Google Scholar 

  43. Roux P, Jeanteur P, Piechaczyk M, et al. A versatile and potentially general approach to the targeting of specific cells by means of major histocompatibility complex class I and class II antigens by mouse ecotropic murine leukaemia virus-derived viruses. Proc Natl Acad Sci USA 1989; 86: 9079–83

    Article  PubMed  CAS  Google Scholar 

  44. Legrain P, Goud B, Butin G. Increase retroviral infection in vitro by the binding of antiretroviral antibodies. J Virol 1986; 60: 1141–4

    PubMed  CAS  Google Scholar 

  45. Etienne-Julan M, Roux P, Carillo S, et al. The efficiency of cell targeting by recombinant retroviruses depends on the nature of the receptor and the composition of the artificial cell-virus linker. J Gen Virol 1992; 73: 3251–5

    Article  PubMed  CAS  Google Scholar 

  46. Cosset FL, Russel SJ. Targeting retrovirus entry. Gene Ther 1996; 3: 946–56

    PubMed  CAS  Google Scholar 

  47. Peng KW, Morling FJ, Cosset FL, et al. A gene delivery system activatable by disease-associated metalloproteinases. Hum Gene Ther 1997; 8: 729–38

    Article  PubMed  CAS  Google Scholar 

  48. Valsesia-Wittman S, Morling FJ, Hatziioannou T, et al. Receptor co-operation in retrovirus entry: recruitment of an auxiliary entry mechanism after retargeted binding. EMBO J 1997; 16: 1214–23

    Article  Google Scholar 

  49. Peng KW, Morling FJ, Cosset FL, et al. Retroviral gene delivery system activatable by plasmin. Tumour Targeting 1998; 3: 112–20

    CAS  Google Scholar 

  50. Peng KW, Vile RG, Cosset FL, et al. Selective transduction of protease-rich tumours by matrix-metalloproteinase-targeted retroviral vectors. Gene Ther 1999; 6: 1552–7

    Article  PubMed  CAS  Google Scholar 

  51. Burns JC, Friedman T, Driever W, et al. Vesicular stomatitis virus G protein pseudotyped retroviral vectors: concentration to high titre and efficient gene transfer into mammalian cells. Proc Natl Acad Sci U S A 1993; 90: 8033–7

    Article  PubMed  CAS  Google Scholar 

  52. Friedman T, Yee JK. Pseudotyped retroviral vectors for studies of human gene therapy. Nat Med 1995; 1: 275–7

    Article  Google Scholar 

  53. Landau NR, Littman DR. Packaging system for rapid production of murine leukaemia virus vectors with variable tropism. J Virol 1992; 5110–3

  54. Pear WS, Nolan GP, Scott ML, et al. Production of helper-free retroviruses by transient transfection. Proc Natl Acad Sci U S A 1993; 90: 8392–6

    Article  PubMed  CAS  Google Scholar 

  55. Soneoka Y, Cannon PM, Ramsdale EE, et al. A transient three-plasmid expression system for the production of high titre retroviral vectors. Nucleic Acids Res 1995; 23: 628–33

    Article  PubMed  CAS  Google Scholar 

  56. Takeuchi Y, Cosst FL, Lachmann PJ, et al. Type C retrovirus inactivation by human complement is determined by both the viral genome and producer cell. J Virol 1993; 86: 8001–7

    Google Scholar 

  57. Cosset FL, Takeuchi Y, Battini JL, et al. High-titre packaging cells producing recombinant retroviruses resistant to human serum. J Virol 1995; 69: 7430–6

    PubMed  CAS  Google Scholar 

  58. Weinberg JB, Matthews, Cullen BR, et al. Productive human immunodeficiency virus type 1 (HIV-1) infection in non-proliferating human monocytes. J Exp Med 1991; 174: 1477–82

    Article  PubMed  CAS  Google Scholar 

  59. Lewis P, Hensel M, Emerman M. Human immunodeficiency virus infection of cells arrested in the cell cycle. EMBO J 1992; 11: 3053–8

    PubMed  CAS  Google Scholar 

  60. Gallay P, Swingler S, Song J, et al. HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 1995; 83: 569–76

    Article  PubMed  CAS  Google Scholar 

  61. Kim VN, Mitrophanous K, Kingsman SM, et al. Minimal requirement for lentivirus vector based on human immunodeficiency virus type 1. J Virol 1998; 72: 811–6

    PubMed  CAS  Google Scholar 

  62. Naldini L, Blomer U, Gallat P, et al. in vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996; 272: 263–7

    Article  PubMed  CAS  Google Scholar 

  63. Zufferey R, Nagy D, Mandel RJ, et al. Multiple attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 1997; 15: 871–5

    Article  PubMed  CAS  Google Scholar 

  64. Blomer U, Naldini L, Kafri T, et al. Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector. J Virol 1997; 71: 6641–9

    PubMed  CAS  Google Scholar 

  65. Brenner MK. Autologous bone marrow transplant for children with acute myelogenous leukaemia in first complete remission: use of marker genes to investigate the biology of marrow reconstitution and the mechanism of relapse. Hum Gene Ther 1991; 2: 137–59

    Article  Google Scholar 

  66. Brenner MK. A phase I trial of high dose carboplatin and etoposide with autologous marrow support for treatment of stage D neuroblastoma in first remission: use of marker genes to investigate the biology of marrow reconstitution and the mechanism of relapse. Hum Gene Ther 1991; 2: 257–72

    Article  Google Scholar 

  67. Deisseroth AB. Autologous bone marrow transplantation for chronic myelogenous leukaemia in which retroviral markers are used to discreminate between relapse which arises from genetic disease remaining after preoperative therapy versus relapse due to residual leukaemic cells in autologous marrow: a pilot trial. Hum Gene Ther 1991; 2: 359–76

    Article  Google Scholar 

  68. Anderson WE. Human gene therapy. Science 1992; 256: 808–13

    Article  PubMed  CAS  Google Scholar 

  69. Rosenberg SA. Immunisation of cancer patients using autologous cancer cells modified by insertion of the gene for the tumour necrosis factor. Hum Gene Ther 1992; 3: 57–73

    Article  Google Scholar 

  70. Gansbacher B, Zier K, Cronin K, et al. Retroviral gene transfer induced constitutive expression of interleukin-2 or interferongamma in irradiated human melanoma cells. Blood 1992; 80: 2817–25

    PubMed  CAS  Google Scholar 

  71. Brenner M, Furman WL, Santana VM, et al. Phase I study of cytokine gene modified autologous neuroblastoma cells for treatment of relapsed/refractory neuroblastoma. Hum Gene Ther 1992; 3: 665–76

    Article  Google Scholar 

  72. Oldfield EH, Ram Z. Gene therapy for the treatment of brain tumours using intratumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum Gene Ther 1993; 4: 60–9

    Article  Google Scholar 

  73. Shand N, Weber F, Mariani L, et al. A phase 1–2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumour transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. Hum Gene Ther 1999; 10: 2325–35

    Article  PubMed  CAS  Google Scholar 

  74. Blease RM, Culver KW, Miller AD, et al. T lymphocytes-directed gene therapy for ADA-SCID: initial trial results after 4 years. Sience 1995; 270: 475–80

    Article  Google Scholar 

  75. Kohn DB, Hershfield MS, Carbonaro D, et al. T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates. Nat Med 1998; 4: 775–80

    Article  PubMed  CAS  Google Scholar 

  76. Nimgaonkar M, Mierski J, Beeler M, et al. Cytokine mobilisation of peripheral blood cells in patients with Gaucher disease with a view to gene therapy. Exp Hematol 1995; 23: 1633–41

    PubMed  CAS  Google Scholar 

  77. Schuening F, Longo WL, Atkinson ME, et al. Retrovirus-mediated transfer of the cDNA for human glucocerebrosidase into peripheral blood repopulating cells of patients with Gaucher’s disease. Hum Gene Ther 1997; 8: 2143–60

    Article  PubMed  CAS  Google Scholar 

  78. Barranger JA, Rice EO, Dunigan J. Gaucher’s disease: studies of gene transfer to hematopoietic cells. Baillieres Clin Hematol 1997; 10: 765–78

    Article  CAS  Google Scholar 

  79. Faibairn LJ, Lashford LS, Spooncer E, et al. Towards gene therapy of Hurler syndrome. Cas Lek Cesk 1997; 136: 27–31

    Google Scholar 

  80. Fu KL, Foe JR, Joenje H, et al. Functional correction of Fanconi anaemia group A hematopoietic cells by retroviral gene transfer. Blood 1997; 90: 3296–303

    PubMed  CAS  Google Scholar 

  81. Liu JM, Kim S, Read EJ, et al. Engraftment of hematopoietic progenitor cells transduced with the Fanconi anaemia group C gene (FANCC). Hum Gene Ther 1999; 10: 2337–46

    Article  PubMed  CAS  Google Scholar 

  82. Mollier P, Bohl D, Heard JM, et al. Correction of lysosomal storage in the liver and spleen of MPS VII mice by manipulation of genetically modified skin fibroblasts. Nat Genet 1993; 4: 154–9

    Article  Google Scholar 

  83. Lou DR, Zhou JM, Zheng B, et al. Stage I clinical trial of gene therapy for hemophilia B. Sci China B 1993; 36: 1342–51

    Google Scholar 

  84. Grossman M, Rader DJ, Muller DWM, et al. A pilot study of ex vivo gene therapy for homozygous familial hyperchlesterinemia. Nat Med 1995; 1: 1148–54

    Article  PubMed  CAS  Google Scholar 

  85. Enders JF, Bell JA, Dingle JH, et al. ‘Adenovirus ‘group name proposed for new respiratory tract viruses. Science 1956; 124: 119–20

    Article  PubMed  CAS  Google Scholar 

  86. Ballay A, Levrero M, Buendia MA, et al. In vitro and in vivo synthesis of the hepatitis B virus surface antigen and of the receptor for polymerized human serum albumin from recombinant human adenovirus. EMBO J 1985; 4: 3861–5

    PubMed  CAS  Google Scholar 

  87. Karlsson S, Van Doren K, Schweiger SG, et al. Stable gene transfer and tissue-specific expression of a human globin gene using adenoviral vectors. EMBO J 1985; 5: 2377–85

    Google Scholar 

  88. Graham FL, Smiley J, Russell WC, et al. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 1977; 36: 59–74

    Article  PubMed  CAS  Google Scholar 

  89. Yei S, Mittereder N, Tang K, et al. Adenovirus-mediated gene transfer for cystic fibrosis: quantitative evaluation of repeated in vivo vector administration to the lung. Nat Genet 1994; 8: 42–51

    Article  Google Scholar 

  90. Yang Y, Wilson JM. Clearance of adenovirus-infected hepatocytes by MHC class I-restricted CD4+ CTLs in vivo. J Immunol 1995; 155: 2564–70

    PubMed  CAS  Google Scholar 

  91. Yang Y, Su Q, Wilson JM. Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs. J Virol 1996; 70: 7209–12

    PubMed  CAS  Google Scholar 

  92. Yang Y, Nunes FA, Berencsi K, et al. Inactivation of E2A in recombinant adenovirus improves transgene persistance and decreases inflammatory response in mouse liver. Proc Natl Acad Sci U S A 1994; 7: 362–9

    CAS  Google Scholar 

  93. Dedieu JF, Vigne E, Torrent C, et al. Long term geen delivery into the livers of immunocompetent mice with E1/E4-defective adenoviruses. J Virol 1997; 71: 4626–37

    PubMed  CAS  Google Scholar 

  94. Morsy MA, Caskey CT. Expanded-capacity adenoviral vectors-the helper-dependent vectors. Mol Med Today 1999; 5: 18–24

    Article  PubMed  CAS  Google Scholar 

  95. Vilquin JT, Guerette B, Kinoshita I, et al. FK506 immunosuppression to control the immune reactions triggered by first-generation adenovirus-mediated gene transfer. Hum Gene Ther 1995; 6: 1391–401

    Article  PubMed  CAS  Google Scholar 

  96. Lei D, Lehmann M, Shellito JE, et al. Nondepleting anti-CD4-antibody treatment prolongs lung-directed E1-deletd adenovirus-mediated gene expression in rats. Hum Gene Ther 1996; 7: 2273–9

    Article  PubMed  CAS  Google Scholar 

  97. Lochmuller H, Petrof RJ, Pari G, et al. Transient immunosuppression by FK506 permits a sustained high-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscles of adult dystrophic (mdx) mice. Gene Ther 1996; 3: 706–16

    PubMed  CAS  Google Scholar 

  98. Kochanek S, Clemens PR, Mitani K, et al. A new adenoviral vector: replacement of all viral coding sequences with 28 kb of DNA independently expressing both full-length dystrophin and β-galactosidase. Proc Natl Acad Sci U S A 1996; 93: 5731–6

    Article  PubMed  CAS  Google Scholar 

  99. Krishna J, Choi H, Burda J, et al. Recombinant adenovirus deleted of all viral genes for gene therapy of cystic fibrosis. J Virol 1996; 217: 11–22

    Article  Google Scholar 

  100. Bischoff JR, Kirn DH, Williams A, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumour cells. Science 1996; 274: 373–6

    Article  PubMed  CAS  Google Scholar 

  101. Reynolds PN, Feng M, Curiel DT. Chimeric viral vectors-the best of both worlds? Mol Med Today 1999; 5: 25–31

    Article  PubMed  CAS  Google Scholar 

  102. Bilbao G, Feng M, Rancourt C, et al. Adenoviral/retroviral chimeras: a novel strategy to achieve high-efficiency stable transduction in vivo. FASEB J 1997; 11: 624–34

    PubMed  CAS  Google Scholar 

  103. Gall J, Kass-Eisler A, Leinwand L, et al. Adenovirus type 5 and type 7 capsid chimera: fibre replacement alters receptor tropism without affecting primary immune neutralisation epitopes. J Virol 1996; 70: 2116–23

    PubMed  CAS  Google Scholar 

  104. Zabner J, Couture LA, Gregory RJ, et al. Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell 1993; 75: 207–16

    Article  PubMed  CAS  Google Scholar 

  105. Knowles MR, Hohnecker K, Zhou Z, et al. A controlled study of adenoviral vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N Engl J Med 1995; 333: 823–31

    Article  PubMed  CAS  Google Scholar 

  106. Bellon G, Michel-Calemard L, Thouvenot D, et al. Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial. Hum Gene Ther 1997; 8: 15–25

    Article  PubMed  CAS  Google Scholar 

  107. Batshaw ML, Wilson JM, Yudkoff M, et al. Recombinant adenovirus gene transfer in adults with partial ornithine transcarbamylase deficiency (OTCD). Hum Gene Ther 1999; 10: 2419–37

    Article  PubMed  CAS  Google Scholar 

  108. Ye X, Robinson MB, Batshaw ML, et al. Prolongend metabolic correction in adult ornithine transcarboxylase — deficient mice with adenoviral vectors. J Biol Chem 1996; 271: 3639–46

    Article  PubMed  CAS  Google Scholar 

  109. Isner JM, Walsh K, Symes J, et al. Arterial gene therapy for therapeutic angiogenesis in patients with peripheral artery disease. Circulation 1995; 91: 2687–92

    Article  PubMed  CAS  Google Scholar 

  110. Freeman SM, Abboud CN, Whartenby KA, et al. The ‘bystander effect’: tumour regression when a fraction of the tumour mass is genetically modified. Cancer Res 1993; 53: 5274–83

    PubMed  CAS  Google Scholar 

  111. Roth JA. Modification of tumour suppressor gene expression and induction of apoptosis in non-small cell lung cancer (NSCLC) with an adenovirus vector expressing wild-type p53 and cisplatin. Hum Gene Ther 1996; 7: 1013–30

    Article  PubMed  CAS  Google Scholar 

  112. Heise C, Sampson-Johannes A, Williams A, et al. ONYX-015, an E1B gene-attenuated adenovirus, causes tumour-specific cytolysis and antitumoural efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 1997; 3: 639–45

    Article  PubMed  CAS  Google Scholar 

  113. Kirn D, Hermiston T, McCormick F. Onyx-15: clinical data are encouraging. Nat Med 1998; 4: 1341–2

    Article  PubMed  CAS  Google Scholar 

  114. Blacklow NR, Hoggan MD, Kapikian AZ, et al. Epidemiology of adenovirus-associated virus infection in a nursey population. Am J Epidemiol 1968; 88: 368–78

    PubMed  CAS  Google Scholar 

  115. Fisher KJ, Gao GP, Weitzman MD, et al. Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis. J Virol 1996; 70: 520–32

    PubMed  CAS  Google Scholar 

  116. Gao GP, Qu G, Faust LZ, et al. High-titer adeno-associated viral vectors from a Rep/Cap cell line and hybrid shuttle virus. Hum Gene Ther 1998; 9: 2353–62

    Article  PubMed  CAS  Google Scholar 

  117. Inoue N, Russell DW. Packaging cells based on inducible gene amplification for the production of adeno-associated virus vectors. J Virol 1998; 72: 7024–31

    PubMed  CAS  Google Scholar 

  118. Matsushita T, Elliger S, Elliger C, et al. Adeno-associated virus vectors can be efficiently produced without helper virus. Gene Ther 1998; 5: 938–45

    Article  PubMed  CAS  Google Scholar 

  119. Xiao X, Li J, Samulski RJ. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol 1998; 72: 2224–32

    PubMed  CAS  Google Scholar 

  120. Kotin RM, Linden RM, Berns KI. Characterisation of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO J 1992; 11: 5071–8

    PubMed  CAS  Google Scholar 

  121. Dong JY, Fan PD, Frizell RA. Quantitative analysis of the packaging capacity of recombinant adeno-associated virus. Hum Gene Ther 1996; 71: 3299–306

    Google Scholar 

  122. Zhou SZ, Cooper S, Kang LY, et al. Adeno-associated virus2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood. J Exp Med 1994; 179: 1867–75

    Article  PubMed  CAS  Google Scholar 

  123. Kaplittmg, Leone P, Samulski RJ, et al. Long term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet 1994; 8: 148–54

    Article  Google Scholar 

  124. Ali RR, Reichel MB, Thrasher AJ, et al. Gene transfer into the mouse retina mediated by an adeno-associated viral vector. Hum Mol Genet 1996; 5: 591–4

    Article  PubMed  CAS  Google Scholar 

  125. Nakai H, Herzog RW, Hagstrom JN, et al. Adeno-associated viral vector-mediated gene transfer of human blood coagulation factor IX into mouse liver. Blood 1998; 91: 4600–7

    PubMed  CAS  Google Scholar 

  126. Fisher KJ, Jooss K, Alston J, et al. Recombinant adeno-associated virus for muscle directed gene therapy. Nat Med 1997; 3: 306–12

    Article  PubMed  CAS  Google Scholar 

  127. Koeberl DD, Alexander IE, Halbert CL, et al. Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors. Proc Natl Acad Sci U S A 1997; 94: 1426–31

    Article  PubMed  CAS  Google Scholar 

  128. Hallek M, Wendtner CM. Recombinant adeno-associated virus (rAAV) vectors for somatic gene therapy: recent advances and potential clinical applications. Cytokines Mol Ther 1996; 2: 69–79

    PubMed  CAS  Google Scholar 

  129. Fan DS, Ogawa M, Fujimoto KI, et al. Behavioural recovery in 6-hydroxydopamine lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors. Hum Gene Ther 1998; 9: 2527–35

    Article  PubMed  CAS  Google Scholar 

  130. Snyder RO, Miao C, Meuse L, et al. Correction of hemophilia B in canine and murine models using recombinant adeno-associated virus vectors. Nat Med 1999; 5: 64–70

    Article  PubMed  CAS  Google Scholar 

  131. Wang L, Takabe K, Bidlingmaier SM, et al. Sustained correction of bleeding disorder in hemophilia B mice by gene therapy. Proc Natl Acad Sci U S A 1999; 96: 3906–10

    Article  PubMed  CAS  Google Scholar 

  132. Daly TM, Vogler C, Levy B, et al. Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease. Proc Natl Acad Sci U S A 1999; 96: 2296–300

    Article  PubMed  CAS  Google Scholar 

  133. Song S, Morgan M, Ellis T, et al. Sustained secretion of human alpha-l-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc Natl Acad Sci U S A 1998; 95: 14384–8

    Article  PubMed  CAS  Google Scholar 

  134. Zhou S, Murphy JE, Escobedo JA, et al. Adeno-associated virus-mediated delivery of erythropoietin leads to sustained elevation of hematocrit in nonhuman primates. Hum Gene Ther 1998; 5: 665–70

    CAS  Google Scholar 

  135. Wagner JA, Moran ML, Messner AH, et al. A phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients with cystic fibrosis. Hum Gene Ther 1998; 9: 889–90

    Article  PubMed  CAS  Google Scholar 

  136. Wagner JA, Reynolds T, Moran ML, et al. Efficient and persistant gene transfer of AAV-CFTR in maxillary sinus. Lancet 1998; 351: 1702–3

    Article  PubMed  CAS  Google Scholar 

  137. Wu N, Watkins SC, Schaffer PA, et al. Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27 and ICP22. J Virol 1996, 70: 6358–69

    PubMed  CAS  Google Scholar 

  138. Chou J, Kern ER, Whitley RJ, et al. Mapping of herpes simplex virus-1 neurovirulence to γ134.5, a gene nonessential for growth in culture. Science 1990; 250: 1262–6

    Article  PubMed  CAS  Google Scholar 

  139. Dobson AT, Margolis TP, Sedarati F, et al. A latent, nonpathogenic HSV-1-derived vector stably expressess beta-galactosidase in mouse neurons. Neuron 1990; 5: 353–60

    Article  PubMed  CAS  Google Scholar 

  140. Wolfe JH, Deshmane SL, Fraser NW. Herpesvirus vector gene transfer and expression of beta-glucuronidase in the central nervous system of MPSVII mice. Nat Genet 1992; 1: 379–84

    Article  PubMed  CAS  Google Scholar 

  141. Miyanohara A, Johnson PA, Elam RL, et al. Direct gene transfer to the liver with herpes simplex virus type 1 vectors: transient production of physioligically relevant levels of circulating factor IX. New Biol 1992; 4: 238–46

    PubMed  CAS  Google Scholar 

  142. During MJ, Naegele JR, O’Malley KL, et al. Long term behavioural recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase. Science 1994; 266: 1399–403

    Article  PubMed  CAS  Google Scholar 

  143. Martuza RL, Malick A, Markert JM, et al. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 1991; 252: 854–6

    Article  PubMed  CAS  Google Scholar 

  144. Pyles RB, Warnick RE, Chalk CL, et al. A novel multiply-mutated HSV-1 strain for the treatment of human brain tumours. Hum Gene Ther 1997; 8: 533–44

    Article  PubMed  CAS  Google Scholar 

  145. Boviatsis EJ, Park JS, Sena-Esteves M, et al. Long term survival of rats harbouring brain neoplasms treated with ganciclovir and herpes simplex virus vector that retains an active thymidine kinase gene. Cancer Res 1994; 54: 5745–61

    PubMed  CAS  Google Scholar 

  146. Mineta T, Rabkin SD, Yazaki T, et al. Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat Med 1995; 1: 938–43

    Article  PubMed  CAS  Google Scholar 

  147. Kramm CM, Chase M, Herrlinger U, et al. Therapeutic efficiency and safety of a second-generation replication-conditional HSV-1 vector for brain tumour gene therapy. Hum Gene Ther 1997; 8: 2057–68

    Article  PubMed  CAS  Google Scholar 

  148. Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination and safety. Proc Natl Acad Sci U S A 1996; 93: 11341–8

    Article  PubMed  CAS  Google Scholar 

  149. Falkner FG, Moss B. Transient dominant selection of recombinant vaccinia viruses. J Virol 1990; 64: 3108–11

    PubMed  CAS  Google Scholar 

  150. Wyatt LS, Shors ST, Murphy BR, et al. Development of a replication — deficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model. Vaccine 1996; 14: 1451–8

    Article  PubMed  CAS  Google Scholar 

  151. Paoletti E. Applications of poxvirus vectors to vaccination: an update. Proc Natl Acad Sci U S A 1996; 93: 11349–53

    Article  PubMed  CAS  Google Scholar 

  152. Gu SY, Huang TM, Ruan L, et al. First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen. Dev Biol Stand 1995; 84: 171–7

    PubMed  CAS  Google Scholar 

  153. Fries LF, Tartaglia J, Taylor J, et al. Human safety and immunogenicity of a canarypox-rabies glycoprotein recombinant vaccine: an alternative poxvirus vector system. Vaccine 1996; 14: 428–34

    Article  PubMed  CAS  Google Scholar 

  154. McAneny D, Ryan CA, Beazley RM, et al. Results of a phase I trial of a recombinant vaccinia virus that expresses carcinoembryonic antigen in patients with advanced colorectal cancer. Ann Surg Oncol 1996; 3: 395–500

    Article  Google Scholar 

  155. Borysiewicz LK, Fiander A, Nimako M, et al. A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 1996; 347: 1523–7

    Article  PubMed  CAS  Google Scholar 

  156. Nimako M, Fiander AM, Wilkinson GW, et al. Human papillomavirus-specific cytotoxic T lymphocytes in patients with cervical intraepithelial neoplasia grade III. Cancer Res 1997; 57: 4855–61

    PubMed  CAS  Google Scholar 

  157. Mecsas J, Sugden B. Replication of plasmids derived from bovine papilloma virus type 1 and Epstein-Barr virus in cell in culture. Annu Rev Cell Biol 1987; 3: 87–108

    Article  PubMed  CAS  Google Scholar 

  158. Sun TQ, Fenstermacher DA, Voss JMH. Human artificial episomal chromosomes for cloning large DNA fragment in human cells. Nat Genet 1994; 8: 33–42

    Article  PubMed  CAS  Google Scholar 

  159. Calos MR. Stability without a centromere. Proc Natl Acad Sci U S A 1998; 95: 4084–5

    Article  PubMed  CAS  Google Scholar 

  160. Lei DC, Kunzelmann K, Koslowsky T, et al. Episomal expression of wild-type CFTR corrects cAMP-dependent chloride transport in respiratory epithelial cells. Gene Ther 1996; 3: 427–36

    PubMed  CAS  Google Scholar 

  161. Hirai H, Satoh E, Osawa M, et al. Use of EBV-based vector/ HVJ-liposome complex vector for targeted gene therapy of EBV-associated neoplasms. Biochem Biophys Res Commun 1997; 241: 112–8

    Article  PubMed  CAS  Google Scholar 

  162. Liljeström P, Garoff H. A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology 1993; 9: 1356–61

    Google Scholar 

  163. Xiong C, Levis R, Shen P, et al. Sindbis virus: an efficient broad host range vector for gene expression in animal cells. Science 1989; 243: 1188–91

    Article  PubMed  CAS  Google Scholar 

  164. Davis NL, Willis LW, Smith JF, et al. In vitro synthesis of infectious Venezulean equine encephalitis virus RNA from a cDNA clone: analysis of a viable deletion mutant. Virology 1989; 171: 189–204

    Article  PubMed  CAS  Google Scholar 

  165. Davis NL, Brown KW, Johnston RE. A viral vaccine vector that expresses foreign genes in lymph nodes and protects against mucosal chellenge. J Virol 1996; 70: 3781–7

    PubMed  CAS  Google Scholar 

  166. Caley IJ, Betts MR, Irlbeck DM. Humoral, mucosal and cellular immunity in response to a human immunodeficiecy virus type 1 imunogen expressed by a Venezulean equine encephalitis virus vacine vector. J Virol 1997; 71: 3031–8

    PubMed  CAS  Google Scholar 

  167. Mocarski ES, Kemble GW, Lyle JM, et al. A deletion mutant in the human cytomegalovirus gene encoding IE1491a is replication defective due to a failure in autoregulation. Proc Natl Acad Sci U S A 1996; 93: 11321–6

    Article  PubMed  CAS  Google Scholar 

  168. Palese P, Zheng H, Engelhardt OG, et al. Negative-strand RNA viruses: genetic engineering and applications. Proc Natl Acad Sci U S A 1996; 93: 11354–8

    Article  PubMed  CAS  Google Scholar 

  169. Duboise SM, Guo J, Desrosiers RC, et al. Use of a virion DNA as a cloning vector for the construction of mutant and recombinant herpesviruses. Proc Natl Acad Sci U S A 1996; 93: 11389–94

    Article  PubMed  CAS  Google Scholar 

  170. Medin JA, Karlsson S. Viral vectors for gene therapy of hematopoietic cells. Immunotechnol 1997; 3: 3–19

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wolfgang Walther.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walther, W., Stein, U. Viral Vectors for Gene Transfer. Drugs 60, 249–271 (2000). https://doi.org/10.2165/00003495-200060020-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200060020-00002

Keywords

Navigation