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Vectors for the treatment of autoimmune disease

Abstract

Gene therapy has been applied in a variety of experimental models of autoimmunity with some success. In this article, we outline recent developments in gene therapy vectors, discuss advantages and disadvantages of each, and highlight their recent applications in autoimmune models. We also consider progress in vector targeting and components for regulating transgene expression, which will both improve gene therapy safety and empower gene therapy to fullfil its potential as a therapeutic modality. In conclusion, we consider candidate vectors that satisfy requirements for application in the principal therapeutic strategies in which gene therapy will be applied to autoimmune conditions.

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References

  1. Yovandich J, O'Malley Jr B, Sikes M, Ledley FD . Gene transfer to synovial cells by intra-articular administration of plasmid DNA. Hum Gene Ther 1995; 6: 603–610.

    CAS  PubMed  Google Scholar 

  2. Wolff JA et al. Direct gene transfer into mouse muscle in vivo. Science 1990; 247: 1465–1468.

    Article  CAS  PubMed  Google Scholar 

  3. Mir LM et al. High-efficiency gene transfer into skeletal muscle mediated by electric pulses. Proc Natl Acad Sci USA 1999; 96: 4262–4267.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Ohashi S et al. Successful genetic transduction in vivo into synovium by means of electroporation. Biochem Biophys Res Commun 2002; 293: 1530–1535.

    CAS  PubMed  Google Scholar 

  5. Lin CR et al. Electroporation-mediated pain-killer gene therapy for mononeuropathic rats. Gene Therapy 2002; 9: 1247–1253.

    CAS  PubMed  Google Scholar 

  6. Zhang L, Nolan E, Kreitschitz S, Rabussay DP . Enhanced delivery of naked DNA to the skin by non-invasive in vivo electroporation. Biochim Biophys Acta 2002; 1572: 1–9.

    CAS  PubMed  Google Scholar 

  7. Budker V et al. The efficient expression of intravascularly delivered DNA in rat muscle. Gene Therapy 1998; 5: 272–276.

    CAS  PubMed  Google Scholar 

  8. Prud'homme GJ, Lawson BR, Chang Y, Theofilopoulos AN . Immunotherapeutic gene transfer into muscle. Trends Immunol 2001; 22: 149–155.

    CAS  PubMed  Google Scholar 

  9. Watanabe K et al. Protection against autoimmune myocarditis by gene transfer of interleukin-10 by electroporation. Circulation 2001; 104: 1098–1100.

    CAS  PubMed  Google Scholar 

  10. Martinenghi S et al. Human insulin production and amelioration of diabetes in mice by electrotransfer-enhanced plasmid DNA gene transfer to the skeletal muscle. Gene Therapy 2002; 9: 1429–1437.

    CAS  PubMed  Google Scholar 

  11. Youssef S et al. C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis. J Clin Invest 2000; 106: 361–371.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wildbaum G, Netzer N, Karin N . Plasmid DNA encoding IFN-gamma-inducible protein 10 redirects antigen-specific T cell polarization and suppresses experimental autoimmune encephalomyelitis. J Immunol 2002; 168: 5885–5892.

    CAS  PubMed  Google Scholar 

  13. Fan GC, Singh RR . Vaccination with minigenes encoding V(H)-derived major histocompatibility complex class I-binding epitopes activates cytotoxic T cells that ablate autoantibody-producing B cells and inhibit lupus. J Exp Med 2002; 196: 731–741.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Krieg AM et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374: 546–549.

    Article  CAS  PubMed  Google Scholar 

  15. MacColl G et al. Intramuscular plasmid DNA injection can accelerate autoimmune responses. Gene Therapy 2001; 8: 1354–1356.

    CAS  PubMed  Google Scholar 

  16. Madry H, Trippel SB . Efficient lipid-mediated gene transfer to articular chondrocytes. Gene Therapy 2000; 7: 286–291.

    CAS  PubMed  Google Scholar 

  17. Fellowes R et al. Amelioration of established collagen induced arthritis by systemic IL-10 gene delivery. Gene Therapy 2000; 7: 967–977.

    CAS  PubMed  Google Scholar 

  18. Croxford JL et al. Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA–cationic liposome complex into the central nervous system. J Immunol 1998; 160: 5181–5187.

    CAS  PubMed  Google Scholar 

  19. Koh JJ et al. Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice. Gene Therapy 2000; 7: 2099–2104.

    CAS  PubMed  Google Scholar 

  20. Barnett BG, Crews CJ, Douglas JT . Targeted adenoviral vectors. Biochim Biophys Acta 2002; 1575: 1–14.

    CAS  PubMed  Google Scholar 

  21. Bett AJ, Prevec L, Graham FL . Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 1993; 67: 5911–5921.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Auricchio A et al. Constitutive and regulated expression of processed insulin following in vivo hepatic gene transfer. Gene Therapy 2002; 9: 963–971.

    CAS  PubMed  Google Scholar 

  23. Ghivizzani SC et al. Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor alpha soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects. Proc Natl Acad Sci USA 1998; 95: 4613–4618.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Croxford JL et al. Local gene therapy with CTLA4-immunoglobulin fusion protein in experimental allergic encephalomyelitis. Eur J Immunol 1998; 28: 3904–3916.

    CAS  PubMed  Google Scholar 

  25. Takiguchi M et al. CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice. Life Sci 2000; 66: 991–1001.

    CAS  PubMed  Google Scholar 

  26. Fleck M et al. Treatment of chronic sialadenitis in a murine model of Sjogren's syndrome by local fasL gene transfer. Arthritis Rheum 2001; 44: 964–973.

    CAS  PubMed  Google Scholar 

  27. Matsui Y et al. Blockade of T cell costimulatory signals using adenovirus vectors prevents both the induction and the progression of experimental autoimmune myocarditis. J Mol Cell Cardiol 2002; 34: 279–295.

    CAS  PubMed  Google Scholar 

  28. De Kozak Y et al. Inhibition of experimental autoimmune uveoretinitis by systemic and subconjunctival adenovirus-mediated transfer of the viral IL-10 gene. Clin Exp Immunol 2002; 130: 212–223.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Whalen JD et al. Adenoviral transfer of the viral IL-10 gene periarticularly to mouse paws suppresses development of collagen-induced arthritis in both injected and uninjected paws. J Immunol 1999; 162: 3625–3632.

    CAS  PubMed  Google Scholar 

  30. Song K et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an inhibitor of autoimmune inflammation and cell cycle progression. J Exp Med 2000; 191: 1095–1104.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Miagkov AV et al. NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc Natl Acad Sci USA 1998; 95: 13859–13864.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Marshall E . Gene therapy death prompts review of adenovirus vector. Science 1999; 286: 2244–2245.

    CAS  PubMed  Google Scholar 

  33. Assessment of adenoviral vector safety and toxicity: report of the National Institutes of Health Recombinant DNA Advisory Committee. Hum Gene Ther 2002; 13: 3–13.

  34. Parks RJ et al. A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc Natl Acad Sci USA 1996; 93: 13565–13570.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Hardy S et al. Construction of adenovirus vectors through Cre-lox recombination. J Virol 1997; 71: 1842–1849.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen L, Anton M, Graham FL . Production and characterization of human 293 cell lines expressing the site-specific recombinase Cre. Somat Cell Mol Genet 1996; 22: 477–488.

    CAS  PubMed  Google Scholar 

  37. Schiedner G et al. Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity. Nat Genet 1998; 18: 180–183.

    CAS  PubMed  Google Scholar 

  38. Morral N et al. Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proc Natl Acad Sci USA 1999; 96: 12816–12821.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Kim IH et al. Lifetime correction of genetic deficiency in mice with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci USA 2001; 98: 13282–13287.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Zou L, Zhou H, Pastore L, Yang K . Prolonged transgene expression mediated by a helper-dependent adenoviral vector (hdAd) in the central nervous system. Mol Ther 2000; 2: 105–103.

    CAS  PubMed  Google Scholar 

  41. Kotin RM et al. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 1990; 87: 2211–2215.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Urcelay E et al. Asymmetric replication in vitro from a human sequence element is dependent on adeno-associated virus Rep protein. J Virol 1995; 69: 2038–2046.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Summerford C, Samulski RJ . Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 1998; 72: 1438–1445.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Samulski RJ, Chang LS, Shenk T . Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. J Virol 1989; 63: 3822–3828.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Monahan PE, Samulski RJ . Adeno-associated virus vectors for gene therapy: more pros than cons? Mol Med Today 2000; 6: 433–440.

    CAS  PubMed  Google Scholar 

  46. Zolotukhin S et al. Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Therapy 1999; 6: 973–985.

    CAS  PubMed  Google Scholar 

  47. Rinaudo D et al. Conditional site-specific integration into human chromosome 19 by using a ligand-dependent chimeric adeno-associated virus/Rep protein. J Virol 2000; 74: 281–294.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kaplitt MG et al. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet 1994; 8: 148–154.

    CAS  PubMed  Google Scholar 

  49. Xiao X, Li J, Samulski RJ . Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol 1996; 70: 8098–8108.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Snyder RO et al. Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors. Nat Genet 1997; 16: 270–276.

    CAS  PubMed  Google Scholar 

  51. Flotte TR et al. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc Natl Acad Sci USA 1993; 90: 10613–10617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Brockstedt DG et al. Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration. Clin Immunol 1999; 92: 67–75.

    CAS  PubMed  Google Scholar 

  53. Moskalenko M et al. Epitope mapping of human anti-adeno-associated virus type 2 neutralizing antibodies: implications for gene therapy and virus structure. J Virol 2000; 74: 1761–1766.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Chirmule N et al. Immune responses to adenovirus and adeno-associated virus in humans. Gene Therapy 1999; 6: 1574–1583.

    CAS  PubMed  Google Scholar 

  55. Jindal RM, Karanam M, Shah R . Prevention of diabetes in the NOD mouse by intra-muscular injection of recombinant adeno-associated virus containing the preproinsulin II gene. Int J Exp Diabetes Res 2001; 2: 129–138.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Goudy K et al. Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice. Proc Natl Acad Sci USA 2001; 98: 13913–13918.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Yang Z et al. Suppression of autoimmune diabetes by viral IL-10 gene transfer. J Immunol 2002; 168: 6479–6485.

    CAS  PubMed  Google Scholar 

  58. Lee HC et al. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue. Nature 2000; 408: 483–488.

    CAS  PubMed  Google Scholar 

  59. Goater J et al. Empirical advantages of adeno associated viral vectors in vivo gene therapy for arthritis. J Rheumatol 2000; 27: 983–989.

    CAS  PubMed  Google Scholar 

  60. Zhang HG et al. Adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tumor necrosis factor alpha and reduces arthritis. Hum Gene Ther 2000; 11: 2431–2442.

    CAS  PubMed  Google Scholar 

  61. Cottard V et al. Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis. Gene Therapy 2000; 7: 1930–1939.

    CAS  PubMed  Google Scholar 

  62. Apparailly F et al. Tetracycline-inducible interleukin-10 gene transfer mediated by an adeno-associated virus: application to experimental arthritis. Hum Gene Ther 2002; 13: 1179–1188.

    CAS  PubMed  Google Scholar 

  63. Burton EA et al. Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells 2001; 19: 358–377.

    CAS  PubMed  Google Scholar 

  64. Palmer JA et al. Development and optimization of herpes simplex virus vectors for multiple long-term gene delivery to the peripheral nervous system. J Virol 2000; 74: 5604–5618.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Oligino T et al. Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis. Gene Therapy 1999; 6: 1713–1720.

    CAS  PubMed  Google Scholar 

  66. Wilson SP et al. Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. Proc Natl Acad Sci USA 1999; 96: 3211–3216.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Braz J et al. Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons. J Neurosci 2001; 21: 7881–7888.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Broberg E et al. Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis. Gene Therapy 2001; 8: 769–777.

    CAS  PubMed  Google Scholar 

  69. Furlan R et al. Central nervous system gene therapy with interleukin-4 inhibits progression of ongoing relapsing-remitting autoimmune encephalomyelitis in Biozzi AB/H mice. Gene Therapy 2001; 8: 13–19.

    CAS  PubMed  Google Scholar 

  70. Poliani PL et al. Delivery to the central nervous system of a nonreplicative herpes simplex type 1 vector engineered with the interleukin 4 gene protects rhesus monkeys from hyperacute autoimmune encephalomyelitis. Hum Gene Therapy 2001; 12: 905–920.

    CAS  Google Scholar 

  71. Ruffini F et al. Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice. Gene Therapy 2001; 8: 1207–1213.

    CAS  PubMed  Google Scholar 

  72. Goss JR et al. Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. Diabetes 2002; 51: 2227–2232.

    CAS  PubMed  Google Scholar 

  73. Kurian KM, Watson CJ, Wyllie AH . Retroviral vectors. Mol Pathol 2000; 53: 173–176.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Kay MA, Glorioso JC, Naldini L . Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 2001; 7: 33–40.

    CAS  PubMed  Google Scholar 

  75. Tarner I, Fathman C . The potential for gene therapy in the treatment of autoimmune disease. Clin Immunol 2002; 104: 204.

    CAS  PubMed  Google Scholar 

  76. Boyle DL et al. Intra-articular IL-4 gene therapy in arthritis: anti-inflammatory effect and enhanced th2 activity. Gene Therapy 1999; 6: 1911–1918.

    CAS  PubMed  Google Scholar 

  77. Morita Y et al. Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis. J Clin Invest 2001; 107: 1275–1284.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Zipris D, Karnieli E . A single treatment with IL-4 via retrovirally transduced lymphocytes partially protects against diabetes in BioBreeding (BB) rats. JOP 2002; 3: 76–82.

    PubMed  Google Scholar 

  79. Nakajima A et al. Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis. J Clin Invest 2001; 107: 1293–1301.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Melo ME et al. Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases. J Immunol 2002; 168: 4788–4795.

    CAS  PubMed  Google Scholar 

  81. Chen C et al. A gene therapy approach for treating T-cell-mediated autoimmune diseases. Blood 2001; 97: 886–894.

    CAS  PubMed  Google Scholar 

  82. Dreja H, Annenkov A, Chernajovsky Y . Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis. Arthritis Rheum 2000; 43: 1698–1709.

    CAS  PubMed  Google Scholar 

  83. Evans CH et al. Clinical trials in the gene therapy of arthritis. Clin Orthop 2000; S300–S307.

    Google Scholar 

  84. Cavazzana-Calvo M et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669–672.

    CAS  PubMed  Google Scholar 

  85. Buckley R . Gene therapy for SCID – a complication after remarkable progress. Lancet 2002; 360: 1185–1186.

    PubMed  Google Scholar 

  86. Ketteler R et al. Enhanced transgene expression in primitive hematopoietic progenitor cells and embryonic stem cells efficiently transduced by optimized retroviral hybrid vectors. Gene Therapy 2002; 9: 477–487.

    CAS  PubMed  Google Scholar 

  87. Daly G, Chernajovsky Y . Recent developments in retroviral-mediated gene transduction. Mol Ther 2000; 2: 423–434.

    CAS  PubMed  Google Scholar 

  88. Naldini L et al. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA 1996; 93: 11382–11388.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Yee JK, Friedmann T, Burns JC . Generation of high-titer pseudotyped retroviral vectors with very broad host range. Methods Cell Biol 1994; 43: 99–112.

    CAS  PubMed  Google Scholar 

  90. Dull T et al. A third-generation lentivirus vector with a conditional packaging system. J Virol 1998; 72: 8463–8471.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Miyoshi H, Takahashi M, Gage FH, Verma IM . Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. Proc Natl Acad Sci USA 1997; 94: 10319–10323.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Kafri T et al. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat Genet 1997; 17: 314–317.

    CAS  PubMed  Google Scholar 

  93. Miyoshi H et al. Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science 1999; 283: 682–686.

    CAS  PubMed  Google Scholar 

  94. Korin YD, Zack JA . 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 1998; 72: 3161–3168.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Srinivasakumar N, Schuening FG . A lentivirus packaging system based on alternative RNA transport mechanisms to express helper and gene transfer vector RNAs and its use to study the requirement of accessory proteins for particle formation and gene delivery. J Virol 1999; 73: 9589–9598.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Zufferey R et al. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 1997; 15: 871–875.

    CAS  PubMed  Google Scholar 

  97. Kim VN, Mitrophanous K, Kingsman SM, Kingsman AJ . Minimal requirement for a lentivirus vector based on human immunodeficiency virus type 1. J Virol 1998; 72: 811–816.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Follenzi A et al. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet 2000; 25: 217–222.

    CAS  PubMed  Google Scholar 

  99. Sirven A et al. The human immunodeficiency virus type-1 central DNA flap is a crucial determinant for lentiviral vector nuclear import and gene transduction of human hematopoietic stem cells. Blood 2000; 96: 4103–4110.

    CAS  PubMed  Google Scholar 

  100. Scherr M et al. Lentiviral gene transfer into peripheral blood-derived CD34+ NOD/SCID-repopulating cells. Blood 2002; 99: 709–712.

    CAS  PubMed  Google Scholar 

  101. Dardalhon V et al. Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap. Gene Therapy 2001; 8: 190–198.

    CAS  PubMed  Google Scholar 

  102. Woods NB et al. Lentiviral gene transfer into primary and secondary NOD/SCID repopulating cells. Blood 2000; 96: 3725–3733.

    CAS  PubMed  Google Scholar 

  103. Douglas J, Kelly P, Evans JT, Garcia JV . Efficient transduction of human lymphocytes and CD34+ cells via human immunodeficiency virus-based gene transfer vectors. Hum Gene Ther 1999; 10: 935–945.

    CAS  PubMed  Google Scholar 

  104. Ramezani A, Hawley TS, Hawley RG . Lentiviral vectors for enhanced gene expression in human hematopoietic cells. Mol Ther 2000; 2: 458–469.

    CAS  PubMed  Google Scholar 

  105. Mikkola H et al. Lentivirus gene transfer in murine hematopoietic progenitor cells is compromised by a delay in proviral integration and results in transduction mosaicism and heterogeneous gene expression in progeny cells. J Virol 2000; 74: 11911–11918.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Demaison C et al. High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter. Hum Gene Ther 2002; 13: 803–813.

    CAS  PubMed  Google Scholar 

  107. Zufferey R, Donello JE, Trono D, Hope TJ . Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Virol 1999; 73: 2886–2892.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Salmon P et al. High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood 2000; 96: 3392–3398.

    CAS  PubMed  Google Scholar 

  109. Zufferey R et al. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 1998; 72: 9873–9880.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Graphodatsky AS et al. Comparative cytogenetics of hamsters of the genus Calomyscus. Cytogenet Cell Genet 2000; 88: 296–304.

    CAS  PubMed  Google Scholar 

  111. Pfeifer A et al. Delivery of the Cre recombinase by a self-deleting lentiviral vector: efficient gene targeting in vivo. Proc Natl Acad Sci USA 2001; 98: 11450–11455.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Cui Y et al. Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells. Blood 2002; 99: 399–408.

    CAS  PubMed  Google Scholar 

  113. Lotti F et al. Transcriptional targeting of lentiviral vectors by long terminal repeat enhancer replacement. J Virol 2002; 76: 3996–4007.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Gao Z et al. High levels of transgene expression following transduction of long-term NOD/SCID-repopulating human cells with a modified lentiviral vector. Stem Cells 2001; 19: 247–259.

    CAS  PubMed  Google Scholar 

  115. Hanawa H et al. Comparison of various envelope proteins for their ability to pseudotype lentiviral vectors and transduce primitive hematopoietic cells from human blood. Mol Ther 2002; 5: 242–251.

    CAS  PubMed  Google Scholar 

  116. Maurice M et al. Efficient gene transfer into human primary blood lymphocytes by surface-engineered lentiviral vectors that display a T cell-activating polypeptide. Blood 2002; 99: 2342–2350.

    CAS  PubMed  Google Scholar 

  117. Klages N, Zufferey R, Trono D . A stable system for the high-titer production of multiply attenuated lentiviral vectors. Mol Ther 2000; 2: 170–176.

    CAS  PubMed  Google Scholar 

  118. Farson D et al. A new-generation stable inducible packaging cell line for lentiviral vectors. Hum Gene Ther 2001; 12: 981–997.

    CAS  PubMed  Google Scholar 

  119. D'Costa J et al. Human immunodeficiency virus type 2 lentiviral vectors: packaging signal and splice donor in expression and encapsidation. J Gen Virol 2001; 82: 425–434.

    CAS  PubMed  Google Scholar 

  120. Matukonis M et al. Development of second- and third-generation bovine immunodeficiency virus-based gene transfer systems. Hum Gene Ther 2002; 13: 1293–1303.

    CAS  PubMed  Google Scholar 

  121. Poeschla EM, Wong-Staal F, Looney DJ . Efficient transduction of nondividing human cells by feline immunodeficiency virus lentiviral vectors. Nat Med 1998; 4: 354–357.

    CAS  PubMed  Google Scholar 

  122. Schnell T et al. Development of a self-inactivating, minimal lentivirus vector based on simian immunodeficiency virus. Hum Gene Ther 2000; 11: 439–447.

    CAS  PubMed  Google Scholar 

  123. Duisit G et al. Five recombinant simian immunodeficiency virus pseudotypes lead to exclusive transduction of retinal pigmented epithelium in rat. Mol Ther 2002; 6: 446.

    CAS  PubMed  Google Scholar 

  124. Mangeot PE et al. Development of minimal lentivirus vectors derived from simian immunodeficiency virus (SIVmac251) and their use for gene transfer into human dendritic cells. J Virol 2000; 74: 8307–8315.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Gouze E et al. In vivo gene delivery to synovium by lentiviral vectors. Mol Ther 2002; 5: 397–404.

    CAS  PubMed  Google Scholar 

  126. Pan D et al. Biodistribution and toxicity studies of VSVG-pseudotyped lentiviral vector after intravenous administration in mice with the observation of in vivo transduction of bone marrow. Mol Ther 2002; 6: 19–29.

    CAS  PubMed  Google Scholar 

  127. Follenzi A et al. Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum Gene Ther 2002; 13: 243–260.

    CAS  PubMed  Google Scholar 

  128. VandenDriessche T et al. Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo. Blood 2002; 100: 813–822.

    CAS  PubMed  Google Scholar 

  129. Gallichan WS et al. Lentivirus-mediated transduction of islet grafts with interleukin 4 results in sustained gene expression and protection from insulitis. Hum Gene Ther 1998; 9: 2717–2726.

    CAS  PubMed  Google Scholar 

  130. Woods NB et al. Lentiviral vector transduction of NOD/SCID repopulating cells results in multiple vector integrations per transduced cell: risk of insertional mutagenesis. Blood 2002; 17: 17.

    Google Scholar 

  131. Bukovsky AA, Song JP, Naldini L . Interaction of human immunodeficiency virus-derived vectors with wild-type virus in transduced cells. J Virol 1999; 73: 7087–7092.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Costa GL et al. Targeting rare populations of murine antigen-specific T lymphocytes by retroviral transduction for potential application in gene therapy for autoimmune disease. J Immunol 2000; 164: 3581–3590.

    CAS  PubMed  Google Scholar 

  133. Lavillette D, Russell SJ, Cosset FL . Retargeting gene delivery using surface-engineered retroviral vector particles. Curr Opin Biotechnol 2001; 12: 461–466.

    CAS  PubMed  Google Scholar 

  134. Valsesia-Wittmann S et al. Improvement of retroviral retargeting by using amino acid spacers between an additional binding domain and the N terminus of Moloney murine leukemia virus SU. J Virol 1996; 70: 2059–2064.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Peng KW et al. A gene delivery system activatable by disease-associated matrix metalloproteinases. Hum Gene Ther 1997; 8: 729–738.

    CAS  PubMed  Google Scholar 

  136. Engelstadter M et al. Targeting human T cells by retroviral vectors displaying antibody domains selected from a phage display library. Hum Gene Ther 2000; 11: 293–303.

    CAS  PubMed  Google Scholar 

  137. Russell SJ, Cosset FL . Modifying the host range properties of retroviral vectors. J Gene Med 1999; 1: 300–311.

    CAS  PubMed  Google Scholar 

  138. Peng KW et al. Organ distribution of gene expression after intravenous infusion of targeted and untargeted lentiviral vectors. Gene Therapy 2001; 8: 1456–1463.

    CAS  PubMed  Google Scholar 

  139. Shayakhmetov DM, Papayannopoulou T, Stamatoyannopoulos G, Lieber A . Efficient gene transfer into human CD34(+) cells by a retargeted adenovirus vector. J Virol 2000; 74: 2567–2583.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Rea D et al. Highly efficient transduction of human monocyte-derived dendritic cells with subgroup B fiber-modified adenovirus vectors enhances transgene- encoded antigen presentation to cytotoxic T cells. J Immunol 2001; 166: 5236–5244.

    CAS  PubMed  Google Scholar 

  141. Stecher H, Shayakhmetov DM, Stamatoyannopoulos G, Lieber A . A capsid-modified adenovirus vector devoid of all viral genes: assessment of transduction and toxicity in human hematopoietic cells. Mol Ther 2001; 4: 36–44.

    CAS  PubMed  Google Scholar 

  142. Asada-Mikami R et al. Efficient gene transduction by RGD-fiber modified recombinant adenovirus into dendritic cells. Jpn J Cancer Res 2001; 92: 321–327.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Krasnykh V et al. Genetic targeting of an adenovirus vector via replacement of the fiber protein with the phage T4 fibritin. J Virol 2001; 75: 4176–4183.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Lee LL et al. Identification of synovium-specific homing peptides by in vivo phage display selection. Arthritis Rheum 2002; 46: 2109–2120.

    CAS  PubMed  Google Scholar 

  145. Clackson T . Regulated gene expression systems. Gene Therapy 2000; 7: 120–125.

    CAS  PubMed  Google Scholar 

  146. Gossen M, Bujard H . Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 1992; 89: 5547–5551.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Gossen M et al. Transcriptional activation by tetracyclines in mammalian cells. Science 1995; 268: 1766–1769.

    CAS  PubMed  Google Scholar 

  148. Yao F et al. Tetracycline repressor, tetR, rather than the tetR-mammalian cell transcription factor fusion derivatives, regulates inducible gene expression in mammalian cells. Hum Gene Ther 1998; 9: 1939–1950.

    CAS  PubMed  Google Scholar 

  149. Rivera VM et al. A humanized system for pharmacologic control of gene expression. Nat Med 1996; 2: 1028–1032.

    CAS  PubMed  Google Scholar 

  150. No D, Yao TP, Evans RM . Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci USA 1996; 93: 3346–3351.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Wang Y, O'Malley Jr BW, Tsai SY, O'Malley BW . A regulatory system for use in gene transfer. Proc Natl Acad Sci USA 1994; 91: 8180–8184.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Fussenegger M et al. Streptogramin-based gene regulation systems for mammalian cells. Nat Biotechnol 2000; 18: 1203–1208.

    CAS  PubMed  Google Scholar 

  153. Hofmann A, Nolan GP, Blau HM . Rapid retroviral delivery of tetracycline-inducible genes in a single autoregulatory cassette. Proc Natl Acad Sci USA 1996; 93: 5185–5190.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Iida A, Chen ST, Friedmann T, Yee JK . Inducible gene expression by retrovirus-mediated transfer of a modified tetracycline-regulated system. J Virol 1996; 70: 6054–6059.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Lindemann D, Patriquin E, Feng S, Mulligan RC . Versatile retrovirus vector systems for regulated gene expression in vitro and in vivo. Mol Med 1997; 3: 466–476.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. S AM, Hawkins RE . Efficient transgene regulation from a single tetracycline-controlled positive feedback regulatory system. Gene Therapy 1998; 5: 76–84.

    Google Scholar 

  157. Strathdee CA, McLeod MR, Hall JR . Efficient control of tetracycline-responsive gene expression from an autoregulated bi-directional expression vector. Gene 1999; 229: 21–29.

    CAS  PubMed  Google Scholar 

  158. Reiser J, Lai Z, Zhang XY, Brady RO . Development of multigene and regulated lentivirus vectors. J Virol 2000; 74: 10589–10599.

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Gould DJ et al. A novel doxycycline inducible autoregulatory plasmid which displays “on”/”off” regulation suited to gene therapy applications. Gene Therapy 2000; 7: 2061–2070.

    CAS  PubMed  Google Scholar 

  160. Pollock R et al. Delivery of a stringent dimerizer-regulated gene expression system in a single retroviral vector. Proc Natl Acad Sci USA 2000; 97: 13221–13226.

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Ogueta SB, Yao F, Marasco WA . Design and in vitro characterization of a single regulatory module for efficient control of gene expression in both plasmid DNA and a self-inactivating lentiviral vector. Mol Med 2001; 7: 569–579.

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Bohl D, Heard JM . Modulation of erythropoietin delivery from engineered muscles in mice. Hum Gene Ther 1997; 8: 195–204.

    CAS  PubMed  Google Scholar 

  163. Bohl D, Naffakh N, Heard JM . Long-term control of erythropoietin secretion by doxycycline in mice transplanted with engineered primary myoblasts. Nat Med 1997; 3: 299–305.

    CAS  PubMed  Google Scholar 

  164. Favre D et al. Lack of an immune response against the tetracycline-dependent transactivator correlates with long-term doxycycline-regulated transgene expression in nonhuman primates after intramuscular injection of recombinant adeno-associated virus. J Virol 2002; 76: 11605–11611.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Urlinger S et al. Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity. Proc Natl Acad Sci USA 2000; 97: 7963–7968.

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Forster K et al. Tetracycline-inducible expression systems with reduced basal activity in mammalian cells. Nucleic Acids Res 1999; 27: 708–710.

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Freundlieb S, Schirra-Muller C, Bujard H . A tetracycline controlled activation/repression system with increased potential for gene transfer into mammalian cells. J Gene Med 1999; 1: 4–12.

    CAS  PubMed  Google Scholar 

  168. Salucci V et al. Tight control of gene expression by a helper-dependent adenovirus vector carrying the rtTA2(s)-M2 tetracycline transactivator and repressor system. Gene Therapy 2002; 9: 1415–1421.

    CAS  PubMed  Google Scholar 

  169. Moser S et al. Dual-regulated expression technology: a new era in the adjustment of heterologous gene expression in mammalian cells. J Gene Med 2001; 3: 529–549.

    CAS  PubMed  Google Scholar 

  170. Feldmann M et al. Is NF-kappaB a useful therapeutic target in rheumatoid arthritis? Ann Rheum Dis 2002; 61(Suppl 2): ii13–ii18.

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Pan RY et al. Disease-inducible transgene expression from a recombinant adeno- associated virus vector in a rat arthritis model. J Virol 1999; 73: 3410–3417.

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Pan RY et al. Therapy and prevention of arthritis by recombinant adeno-associated virus vector with delivery of interleukin-1 receptor antagonist. Arthritis Rheum 2000; 43: 289–297.

    CAS  PubMed  Google Scholar 

  173. Varley AW, Geiszler SM, Gaynor RB, Munford RS . A two-component expression system that responds to inflammatory stimuli in vivo. Nat Biotechnol 1997; 15: 1002–1006.

    CAS  PubMed  Google Scholar 

  174. Bakker AC et al. C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene. Arthritis Rheum 2002; 46: 1661–1670.

    CAS  PubMed  Google Scholar 

  175. Miagkov AV, Varley AW, Munford RS, Makarov SS . Endogenous regulation of a therapeutic transgene restores homeostasis in arthritic joints. J Clin Invest 2002; 109: 1223–1229.

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Hollander AP, Corke KP, Freemont AJ, Lewis CE . Expression of hypoxia-inducible factor 1alpha by macrophages in the rheumatoid synovium: implications for targeting of therapeutic genes to the inflamed joint. Arthritis Rheum 2001; 44: 1540–1544.

    CAS  PubMed  Google Scholar 

  177. Shibata T et al. Enhancement of gene expression under hypoxic conditions using fragments of the human vascular endothelial growth factor and the erythropoietin genes. Int J Radiat Oncol Biol Phys 1998; 42: 913–916.

    CAS  PubMed  Google Scholar 

  178. Shibata T, Giaccia AJ, Brown JM . Development of a hypoxia-responsive vector for tumor-specific gene therapy. Gene Therapy 2000; 7: 493–498.

    CAS  PubMed  Google Scholar 

  179. Chen R, Meseck ML, Woo SL . Auto-regulated hepatic insulin gene expression in type 1 diabetic rats. Mol Ther 2001; 3: 584–590.

    CAS  PubMed  Google Scholar 

  180. Thule PM, Liu JM . Regulated hepatic insulin gene therapy of STZ-diabetic rats. Gene Therapy 2000; 7: 1744–1752.

    CAS  PubMed  Google Scholar 

  181. Halban PA, Kahn SE, Lernmark A, Rhodes CJ . Gene and cell-replacement therapy in the treatment of type 1 diabetes: how high must the standards be set? Diabetes 2001; 50: 2181–2191.

    CAS  PubMed  Google Scholar 

  182. Rivera VM et al. Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. Science 2000; 287: 826–830.

    CAS  PubMed  Google Scholar 

  183. Bessis N et al. Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA). Clin Exp Immunol 1999; 117: 376–382.

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Evans CH et al. Results from the first human clinical trial of gene therapy for arthritis. Arthritis Rheum 1999; 42: S170 (Abstract).

    Google Scholar 

  185. Losordo DW et al. Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia. Circulation 2002; 105: 2012–2018.

    CAS  PubMed  Google Scholar 

  186. Isner JM et al. Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg 1998; 28: 964–973; discussion 73–75.

    CAS  PubMed  Google Scholar 

  187. Baumgartner I et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998; 97: 1114–1123.

    CAS  PubMed  Google Scholar 

  188. Zheng C et al. Evaluation of salivary gland acinar and ductal cell-specific promoters in vivo with recombinant adenoviral vectors. Hum Gene Ther 2001; 12: 2215–2223.

    CAS  PubMed  Google Scholar 

  189. Ghazizadeh S, Doumeng C, Taichman LB . Durable and stratum-specific gene expression in epidermis. Gene Therapy 2002; 9: 1278–1285.

    CAS  PubMed  Google Scholar 

  190. Lin MT, Wang F, Uitto J, Yoon K . Differential expression of tissue-specific promoters by gene gun. Br J Dermatol 2001; 144: 34–39.

    CAS  PubMed  Google Scholar 

  191. Lee M, Han S, Ko KS, Kim SW . Cell type specific and glucose responsive expression of interleukin-4 by using insulin promoter and water soluble lipopolymer. J Control Release 2001; 75: 421–429.

    CAS  PubMed  Google Scholar 

  192. Zhou G et al. Three high mobility group-like sequences within a 48-base pair enhancer of the Col2a1 gene are required for cartilage-specific expression in vivo. J Biol Chem 1998; 273: 14989–14997.

    CAS  PubMed  Google Scholar 

  193. Shi N et al. Brain-specific expression of an exogenous gene after i.v. administration. Proc Natl Acad Sci USA 2001; 98: 12754–12759.

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Segovia J, Vergara P, Brenner M . Astrocyte-specific expression of tyrosine hydroxylase after intracerebral gene transfer induces behavioral recovery in experimental parkinsonism. Gene Therapy 1998; 5: 1650–1655.

    CAS  PubMed  Google Scholar 

  195. Triantaphyllopoulos K, Croxford J, Baker D, Chernajovsky Y . Cloning and expression of murine IFN beta and a TNF antagonist for gene therapy of experimental allergic encephalomyelitis. Gene Therapy 1998; 5: 253–263.

    CAS  PubMed  Google Scholar 

  196. Mathisen PM et al. Treatment of experimental autoimmune encephalomyelitis with genetically modified memory T cells. J Exp Med 1997; 186: 159–164.

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Morita A et al. Development of a Langerhans cell-targeted gene therapy format using a dendritic cell-specific promoter. Gene Therapy 2001; 8: 1729–1737.

    CAS  PubMed  Google Scholar 

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Acknowledgements

Financial support was provided by the Arthritis Research Campaign UK (DG) and the Joint Research Board of St Bartholomew's Hospital (PF).

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Gould, D., Favorov, P. Vectors for the treatment of autoimmune disease. Gene Ther 10, 912–927 (2003). https://doi.org/10.1038/sj.gt.3302018

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