Advertisement

Gene Therapy in Organ Transplantation: Applicabilities and Shortcomings

  • John C. Magee
  • Randall S. Sung
  • Jonathan S. Bromberg

Abstract

Gene therapy holds great promise for the treatment of many conditions but it is currently limited by the inability to effectively introduce the transgene into the tissue of interest, as well as low level and transient transgene expression. Furthermore, once long term transgene expression is achieved, it will need to be responsive to regulation via normal homeostatic mechanisms or via pharmacologic means. These hurdles are significant and limit the current application of gene therapy in many areas, but may pose less of an issue in the context of transplantation. Trans-plantation is a relatively unique setting where one might envision gene therapy being applied in situ to the cadaveric donor prior to organ retrieval, or ex vivo prior to implantation of the cells or organ into the recipient, allowing for higher doses of vector to be administered without systemic toxicity. Furthermore, this selective perfusion of the organ ex vivo provides a functional tissue specificity independent of vector design, a current hurdle for in vivo gene therapy in other applications. The transient expression of the transgene, while a shortcoming in applications such as gene replacement therapy, may actually be bene?ficial in the context of transplantation. The limited expression of an immunomodulatory molecule in the microenvironment of the graft may be sufficient to alter the interaction between the donor antigens and the recipient immune system so that a state of donor specific hypores-ponsiveness or functional tolerance is generated.

Keywords

Gene Therapy Gene Transfer Organ Transplantation Allograft Survival Nonviral Vector 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. 1.
    Addison CL, Hitt M, Kunsken D, Graham FL. Comparison of the human versus murine cytomegalovirus immediate early gene promoters for transgene expression by adenoviral vectors. J Gen Virol. 78(Pt 7): 1653–1661, 1997.PubMedGoogle Scholar
  2. 2.
    Adesanya MR, Redman RS, Baum BJ, O’Connell BC. Immediate inflammatory responses to adenovirus-mediated gene transfer in rat salivary glands. Hum Gene Ther. 7(9): 1085–1093, 1996.PubMedCrossRefGoogle Scholar
  3. 3.
    Aihara H, Miyazaki J. Gene transfer into muscle by electroporation in vivo. Nat Biotech 16(9): 867–870, 1998.CrossRefGoogle Scholar
  4. 4.
    Armentano D, Thompson AR, Darlington G, Woo SL. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: Potential for gene therapy of human hemophilia B. Proc Natl Acad Sci USA 87(16):6141–6145, 1990.PubMedCrossRefGoogle Scholar
  5. 5.
    Ballas ZK, Rasmussen WL., Krieg AM. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol. 157(5): 1840–1845, 1996.PubMedGoogle Scholar
  6. 6.
    Banerjee PT, Ierino F, Kaynor GC, Giovino M, Sablinski T, Emery DW, Rosa MD, LeGuern C, Sachs DH, Monroy RL. Retrovirus-mediated gene transfer and expression of swine MHC Class II genes in CD34+ monkey stem cells. Transplant Proc 28(2):747–748, 1996.PubMedGoogle Scholar
  7. 7.
    Boasquevisque CHR, Mora BN, Schmid RA, Lee TC, Nagahiro I, Cooper JD, Patterson GA. Ex vivo adenoviral-mediated gene transfer to lung isografts during cold preservation. Ann Thorac Surg 63(6): 1556–1561, 1997.PubMedCrossRefGoogle Scholar
  8. 8.
    Bohuslav J, Kravchenko VV, Parry GC, Erlich JH., Gerondakis S, Mackman N, Ulevitch RJ. Regulation of an essential innate immune response by the p50 subunit of NF-kappaB. J. Clin Invest. 102(9): 1645–1652, 1998.PubMedCrossRefGoogle Scholar
  9. 9.
    Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, Ponzoni M, Rossini S, Mavilio F, Traversari C et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276(5319): 1719–1724, 1997.PubMedCrossRefGoogle Scholar
  10. 10.
    Bouloc A, Walker P, Grivel JC, Vogel JC, Katz SI. Immunization through dermal delivery of protein-encoding DNA: a role for migratory dendritic cells. Eur. J. Immunol. 29(2):446–454, 1999.PubMedCrossRefGoogle Scholar
  11. 11.
    Brenner MK, Heslop HE, Rill D, Li C, Nilson T, Roberts M, Smith C, Krance R, Rooney C. Gene transfer and bone marrow transplantation. Cold Spring Harb Symp Quant Biol 59:691–697,1994.PubMedCrossRefGoogle Scholar
  12. 12.
    Bromberg JS, DeBruyne LA, Qin L. Interactions between the immune system and gene therapy vectors: Bidirectional regulation of response and expression. Adv Immunol. 69:353–409, 1998.PubMedCrossRefGoogle Scholar
  13. 13.
    Brossart P, Goldrath AW, Butz EA, Martin S, Bevan MJ. Virus-mediated delivery of antigenic epitopes into dendritic cells as a means to induce CTL. J. Immunol. 158(7):3270–3276, 1997.PubMedGoogle Scholar
  14. 14.
    Brough DE, Hsu C, Kulesa VA, Lee GM, Cantolupo LJ, Lizonova A, Kovesdi I. Activation of transgene expression by early region 4 is responsible for a high level of persistent transgene expression from adenovirus vectors in vivo. J. Virol. 71(12):9206–9213, 1997.PubMedGoogle Scholar
  15. 15.
    Burcin MM, Schiedner G, Kochanek S, Tsai SY, O’Malley BW. Adenovirus-mediated regulable target gene expression in vivo. Proc. Natl. Acad Sci USA. 96(2):355–360, 1999.PubMedCrossRefGoogle Scholar
  16. 16.
    Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA. Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope. J. Exp Med. 186(9): 1481–1486, 1997.PubMedCrossRefGoogle Scholar
  17. 17.
    Chahine AA, Yu M, McKernan MM, Stoeckert C, Lau HT. Immunomodulation of pancreatic islet allografts in mice with CTLA4Ig secreting muscle cells. Transplantation. 59(9): 1313–1318, 1995.PubMedGoogle Scholar
  18. 18.
    Chattergoon MA, Robinson TM, Boyer JD, Weiner DB. Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells. J. Immunol. 160(12): 5707–5718, 1998.PubMedGoogle Scholar
  19. 19.
    Chen HH, Mack LM, Choi SY, Ontell M, Kochanek S, Clemens PR. DNA from both high-capacity and first-generation adenoviral vectors remains intact in skeletal muscle. Hum Gene Ther. 10(3):365–373, 1999.PubMedCrossRefGoogle Scholar
  20. 20.
    Chirmule N, Hughes JV, Gao GP, Raper SE, Wilson JM. Role of E4 in eliciting CD4 T-cell and B-cell responses to adenovirus vectors delivered to murine and nonhuman primate lungs. J. Virol. 72(7):6138–6145, 1998.PubMedGoogle Scholar
  21. 21.
    Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV. CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Thl) immunity. J. Exp Med. 186(10):1623–1631, 1997.PubMedCrossRefGoogle Scholar
  22. 22.
    Csete ME, Drazan KE, Van Bree M, Mcintee DF, McBride WH, Bett A, Graham FL, Busuttil RW, Berk AJ, Shaked A. Adenovirus-mediated gene transfer in the transplant setting. I. Conditions for expression of transferred genes in cold-preserved hepatocytes. Transplantation 57:(10) 1502–1507, 1994.PubMedGoogle Scholar
  23. 23.
    DeBruyne LA, Kewang L, Bishop K, Bromberg JS. Gene transfer of virally encoded chemokine agonists, vMIP-II and MC148, prolongs cardiac allograft survival. Transplantation 67(9):S571, 1999.CrossRefGoogle Scholar
  24. 24.
    DeBruyne LA, Magee JC, Buelow R, and Bromberg JS: Gene transfer of immunomodulatory peptides correlates with heme oxygenase-I induction and enhanced allograft survival. Transplantation (in press).Google Scholar
  25. 25.
    Deuschle U, Pepperkok R, Wang F, Giordano TJ, McAllister WT, Ansorge W, Bujard H. Regulated expression of foreign genes in mammalian cells under the control of coliphage T3 RNA polymerase and lac repressor. Proc Natl Acad Sci USA 86(14): 5600–5604, 1989.CrossRefGoogle Scholar
  26. 26.
    De Waal Malefyt R, Haanen J, Spits H, Roncarlol MG, te Velde A, Figdor C, Johnson C, Kastelein R, Yssel H, de Vries JE. Interleulin-10 (IL-10) and viral IL-IO strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via down-regulation of class II major histocompatibility complex expression. J Exp Med 174(4):915–924, 1991.PubMedCrossRefGoogle Scholar
  27. 27.
    Docherty K. Gene therapy for diabetes mellitus. Clinical Science 92(4):321–330, 1997.Google Scholar
  28. 28.
    Drazan KE, Olthoff KM, Wu L, Shen X, Gelman A, Shaked, A. Adenovirus-mediated gene transfer in the transplant setting: early events after orthotopic transplantation of liver allografts expressing TGF-▭1. Transplantation 62(8):1080–1084, 1996.PubMedCrossRefGoogle Scholar
  29. 29.
    Efrat S, Fusco-Demane D, Lemberg H, Erman OA, Wang X. Conditional transformation of a pancreatic ▭-cell line derived from transgenic mice expressing a tetracycline-regulated oncogene. Proc Natl Acad Sci USA 92(8): 3576–3580, 1995a.PubMedCrossRefGoogle Scholar
  30. 30.
    Efrat S, Fejer, Brownlee M, Horwitz MS. Prolonged survival of pancreatic islet allografts mediated by adenovirus immunoregulatory transgenes. Proc Natl Acad Sci USA 92(15):6947–6951, 1995b.PubMedCrossRefGoogle Scholar
  31. 31.
    Eglitis MA, Kantoff P, Gilboa E, Anderson WF. Gene expression in mice after high efficiency retroviral-mediated gene transfer. Science 230(4732): 1395–1398, 1985.PubMedCrossRefGoogle Scholar
  32. 32.
    Elkon KB, Liu CC, Gall JG, Trevejo J, Marino MW, Abrahamsen KA, Song X, Zhou JL, Old U, Crystal RG, Falck-Pedersen E. Tumor necrosis factor alpha plays a central role in immune-mediated clearance of adenoviral vectors. Proc Natl Acad Sci USA. 94(18):9814–9819, 1997.PubMedCrossRefGoogle Scholar
  33. 33.
    Emery DW, Shafer GE, Karson EM, Sachs DH, LeGuern C. Retrovirus-mediated transfer and expression of an allogeneic major histocompatibility complex class II DRB cDNA in swine bone marrow cultures. Blood. 81(9):2460–2465, 1993a.PubMedGoogle Scholar
  34. 34.
    Emery DW, Smith CV, Shafer GE, Karson EM, Sachs DH, LeGuern C. Expression of allogeneic class II cDNA in swine peripheral blood mononuclear cells following retroviral-mediated gene transfer into bone marrow. Transplantation Proc. 25(1 Pt 1): 140–141, 1993b.Google Scholar
  35. 35.
    Emery DW, Sablinski T, Arn JS, LeGuern C, Sachs DH. Bone marrow culture and transduction of stem cells in a miniature swine model. Blood Cells. 20(2–3):498–502, 1994.PubMedGoogle Scholar
  36. 36.
    Fabrega AJ, Fasbender AJ, Struble S, Zabner J. Cationic lipid-mediated transfer of the hIL-10 gene prolongs survival of allogeneic hepatocytes in Nagase analbuminemic rats. Transplantation 62(12): 1866–1871, 1996.PubMedCrossRefGoogle Scholar
  37. 37.
    Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA. 84(21):7413–7417, 1987.PubMedCrossRefGoogle Scholar
  38. 38.
    Ferber S, Beltrande I, Rio H, Johnson JH, Noel RJ, Cassidy LE, Clark S, Becker TC, Hughes SD, Newgard CB. GLUT-2 gene transfer into insulinoma cells confers both low and high affinity glucose-stimulated insulin release. J Biol Chem 269(15):11523–11529, 1994.PubMedGoogle Scholar
  39. 39.
    Fisher KJ, Jooss K, Alston J, Yang Y, Haecker SE, High K, Pathak R, Raper SE, Wilson JM. Recombinant adeno-associated virus for muscle directed gene therapy. Nat Med. 3(3):306–312, 1997.PubMedCrossRefGoogle Scholar
  40. 40.
    Fraser CC, Sykes M, Lee RS, Sachs DH, LeGuern C. Specific unresponsiveness to a retrovirally-transferred class I antigen is controlled through the helper pathway. J. Immunol. 154(4): 1587–1595, 1995.PubMedGoogle Scholar
  41. 41.
    Gainer AL, Korbutt GS, Rajotte RV, Warnock GL, Elliott JF. Expression of CTLA4-Ig by biolistically transfected mouse islets promotes islet allograft survival. Transplantation. 63(7): 1017–1021, 1997.PubMedCrossRefGoogle Scholar
  42. 42.
    Gangappa S, Babu JS, Thomas J, Daheshia M, Rouse BT. Virus-induced immunoinflammatory lesions in the absence of viral antigen recognition. J. Immunol. 161(8):4289–4300, 1998.PubMedGoogle Scholar
  43. 43.
    Ghazizadeh S, Carroll JM, Taichman LB. Repression of retrovirus-mediated transgene expression by interferons: implications for gene therapy. J. Virol. 71(12):9163–9169, 1997.PubMedGoogle Scholar
  44. 44.
    Ghosh-Choudhury G, Graham FL. Stable transfer of a mouse dihydrofolate reductase gene into a deficient cell line using human adenovirus vector. Biochem Biophys Res Comm. 147(3):964–973, 1987.PubMedCrossRefGoogle Scholar
  45. 45.
    Gordon EM, Anderson WF. Gene therapy using retroviral vectors. Curr Opin Biotech 5(6):611–616, 1994.PubMedCrossRefGoogle Scholar
  46. 46.
    Gribaudo G, Ravaglia S, Caliendo A, Cavallo R, Gariglio M, Martinotti MG, Landolfo S. Interferons inhibit onset of murine cytomegalovirus immediate-early gene transcription. Virol. 197(1):303–311, 1993.CrossRefGoogle Scholar
  47. 47.
    Grossman M, Raper SE, Kozarsky K, Stein EA, Engelhardt JF, Muller D, Lupien PJ, Wilson JM. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolemia. Nat Genetics 6(4):335–341, 1994.CrossRefGoogle Scholar
  48. 48.
    Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber R, Chisari FV. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity. 4(1):25–36, 1996.PubMedCrossRefGoogle Scholar
  49. 49.
    Hacker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J. 17(21):6230–6240, 1998.PubMedCrossRefGoogle Scholar
  50. 50.
    Harms JS, Splitter GA. Interferon-gamma inhibits transgene expression driven by SV40 or CMV promoters but augments expression driven by the mammalian MHC I promoter. Hum Gene Ther. 6(10):1291–1297, 1995.PubMedCrossRefGoogle Scholar
  51. 51.
    Hatzoglou M, Lamers W, Bosch F, et al. Hepatic gene transfer in animals using retroviruses containing the promoter from the gene for phosphoenolpyruvate carboxykinase. J. Biol Chem 265(28):17285–17293, 1990.PubMedGoogle Scholar
  52. 52.
    Hottiger MO, Felzien LK, Nabel GJ. Modulation of cytokine-induced HIV gene expression by competitive binding of transcription factors to the coactivator p300. EMBOJ. 17(11):3124–3134, 1998.CrossRefGoogle Scholar
  53. 53.
    Hsu DH, De Waal Malefyt R, Fiorentino DF, Dang MN, Vieira P, DeVries J, Spits H, Mosmann TR, Moore KW. Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. Science 250(4982):830–832, 1990.PubMedCrossRefGoogle Scholar
  54. 54.
    Jooss K, Yang Y, Fisher KJ, Wilson JM. Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J. Virol. 72(5):4212–4223, 1998.PubMedGoogle Scholar
  55. 55.
    Kafri T, Morgan D, Krahl T, Sarvetnick N, Sherman L, Verma I. Cellular immune response to adenoviral vector infected cells does not require de novo viral gene expression: implications for gene therapy. Proc Natl Acad Sci USA. 95(19):11377–11382, 1998.PubMedCrossRefGoogle Scholar
  56. 56.
    Kay MA, Baley P, Rothenberg S, Leland F, Fleming L, Parker Ponder K, Liu T-J, Finegold M, Darlington G, Pokorny W. et al. Expression of human □1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. Proc Natl Acad Sci USA 89(4982): 89–93, 1992.PubMedCrossRefGoogle Scholar
  57. 57.
    Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM. CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma. Proc Natl Acad Sci USA. 93(7):2879–2883, 1996.PubMedCrossRefGoogle Scholar
  58. 58.
    Kozarsky KF, Wilson JM. Gene therapy: adenovirus vectors. Curr Opin Genet Dev. 3(3):499–503, 1993.PubMedCrossRefGoogle Scholar
  59. 59.
    Kuhr T, Dougherty GJ, Klingermann H-G. Transfer of the tumor necrosis factor a gene into hematopoietic progenitor cells as a model for site-specific cytokine delivery after marrow transplantation. Blood 84(9):2966–2970, 1994.PubMedGoogle Scholar
  60. 60.
    Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, Baker JR Jr. Efficient transfer of genetic material into mammalian cells using Starburst polyamidoamine dendrimers. Proc Natl Acad Sci, USA. 93(10):4897–4902, 1996.PubMedCrossRefGoogle Scholar
  61. 61.
    Lau HT, Yu M, Fontana A, Stoeckert CJ Jr. Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science. 273(5271): 109–112, 1996.PubMedCrossRefGoogle Scholar
  62. 62.
    Leiden JM. Beating the odds: a cardiomyocyte cell line at last. J. Clin Invest. 103(5):591–592, 1999.PubMedCrossRefGoogle Scholar
  63. 63.
    Levy AE, Alexander JW. Administration of intragraft interleukin-4 prolongs cardiac allograft survival in rats treated with donor-specific transfusion/cyclosporine. Transplantation. 60(5):405–406, 1995.PubMedCrossRefGoogle Scholar
  64. 64.
    Lieber A, He CY, Meuse L, Schowalter D, Kirillova I, Winther B, Kay MA. The role of Kupffer cell activation and viral gene expression in early liver toxicity after infusion of recombinant adenovirus vectors. J. Virol. 71(11):8798–8807, 1997.PubMedGoogle Scholar
  65. 65.
    Lieber A, He CY, Meuse L, Himeda C, Wilson C, Kay MA. Inhibition of NF-kappaB activation in combination with bcl-2 expression allows for persistence of first-generation adenovirus vectors in the mouse liver. J. Virol. 72(11):9267–9277, 1998.PubMedGoogle Scholar
  66. 66.
    Lin H, Parmacek MS, Morle G, Boiling S, Leiden JM. Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation 82(6):2217–2221, 1990.PubMedCrossRefGoogle Scholar
  67. 67.
    Loser P, Jennings GS, Strauss M, Sandig V. Reactivation of the previously silenced cytomegalovirus major immediate-early promoter in the mouse liver: involvement of NF-kappaB. J. Virol. 72(1): 180–190, 1998.PubMedGoogle Scholar
  68. 68.
    Lucin P, Jonjic S, Messerle M, Polie B, Hengel H, Koszinowski UH. Late phase inhibition of murine cytomegalovirus replication by synergistic action of interferon-gamma and tumour necrosis factor. J. Gen. Virol. 75(Pt 1): 101–110, 1994.PubMedCrossRefGoogle Scholar
  69. 69.
    Lusky M, Christ M, Rittner K, Dieterle A, Dreyer D, Mourot B, Schultz H, Stoeckel F, Pavirani A, Mehtali M. In vitro and in vivo biology of recombinant adenovirus vectors with El, E1/E2A, or E1/E4 deleted. J. Virol. 72(3):2022–2032, 1998.PubMedGoogle Scholar
  70. 70.
    Macfarlane DE, Manzel L. Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds. J. Immunol. 160(3): 1122–1131, 1998.PubMedGoogle Scholar
  71. 71.
    Magee JC, DeBruyne LA, Buelow R, Bromberg JS. Gene transfer of immunosuppressive peptides B2702 and RDP1257 prolongs allograft survival: evidence suggesting a role for heme oxygenase-I. Transplant Proc. 31(1–2):1194, 1999.PubMedCrossRefGoogle Scholar
  72. 72.
    Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata J, Umezawa A, Ogawa S. Cardiomyocytes can be generated from marrow stromal cells in vitro. J. Clin Invest. 103(5):697–705, 1999.PubMedCrossRefGoogle Scholar
  73. 73.
    McCoy RD, Davidson BL, Roessler BJ, Huffnagle GB, Simon RH. Expression of human interleukin-1 receptor antagonist in mouse lungs using a recombinant adenovirus: effects on vector-induced inflammation. Gene Ther 2(7):437–442, 1995.PubMedGoogle Scholar
  74. 74.
    Miyoshi H, Smith KA, Mosier DE, Verma IM, Torbett BE. Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science. 283(5402):682–686, 1999.PubMedCrossRefGoogle Scholar
  75. 75.
    Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 248(4960): 1230–1234, 1990.PubMedCrossRefGoogle Scholar
  76. 76.
    Muruve DA, Barnes MJ, Stillman IE, Liebermann TA. Adenoviral genetherapy leads to rapid induction of multiple chemokines and actue neutrophil-dependent hepatic injury in vivo. Hum Gene Ther. 10(6):965–976, 1999.PubMedCrossRefGoogle Scholar
  77. 77.
    Naldini L, Blomer U, Fallay P, Ory D, Muligan R, Gage FH, Verma IM, and Trono D. In vivo delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272(5259):263–267, 1996.PubMedCrossRefGoogle Scholar
  78. 78.
    Nicolau C, Legrand A, Grosse E. Liposomes as carriers for in vivo gene transfer and expression. Methods Enzymol. 149:157–176, 1987.PubMedCrossRefGoogle Scholar
  79. 79.
    Olszewska-Pazdrak B, Casola A, Saito T, Alam R, Crowe SE, Mei F, Ogra PL, Garofalo RP. Cell-specific expression of RANTES, MCP-1, and MIP-lalpha by lower airway epithelial cells and eosinophils infected with respiratory syncytial virus. J. Virol. 72(6):4756–4764, 1998.PubMedGoogle Scholar
  80. 80.
    Olthoff KM, Da Chen X, Gelman A, Turka L, Shaked A. Adenovirus-mediated gene transfer of CTLA4Ig to liver allografts results in prolonged survival and local Tcellanergy. Transplant Proc 29(1–2):1030–1031, 1997.PubMedCrossRefGoogle Scholar
  81. 81.
    Otake K, Ennist DL, Harrod K, Trapnell BC. Nonspecific inflammation inhibits adenovirus-mediated pulmonary gene transfer and expression independent of specific acquired immune responses. Hum Gene Ther. 9(15):2207–2222, 1998.PubMedCrossRefGoogle Scholar
  82. 82.
    Pan R-Y, Xiao X, Chen S-L, Li J, Lin L-C, Wang H-J, Tsao Y-P. Disease-inducible transgene expression from a recombinant adeno-associated virus vector in a rat arthritis model. J. Virol. 73(4):3410–3417, 1999.PubMedGoogle Scholar
  83. 83.
    Poller W, Schneider-Rasp S, Liebert U, Merklein F, Thalheimer P, Haack A., Schwaab R, Schmitt C, Brackmann HH. Stabilization of transgene expression by incorporation of E3 region genes into an adenoviral factor IX vector and by transient anti-CD4 treatment of the host. Gene Ther. 3(6):521–530, 1996.PubMedGoogle Scholar
  84. 84.
    Porgador A, Irvine KR, Iwasaki A, Barber BH, Restifo NP, Germain RN. Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization. J. Expl Med. 188(6): 1075–1082, 1998.CrossRefGoogle Scholar
  85. 85.
    Presti RM, Pollock JL, Dal Canto AJ, O’Guin AK, Virgin HW 4th. Interferon gamma regulates acute and latent murine cytomegalovirus infection and chronic disease of the great vessels. J. Expl Med. 188(3): 577–588, 1998.CrossRefGoogle Scholar
  86. 86.
    Qin L, Chavin KD, Ding Y, Favarro JP, Woodward JE, Lin J, Tahara H, Robbins P, Shaked A, et al. Multiple vectors effectively achieve gene transfer in a murine cardiac transplantation model: Immunosuppression with TGF-ßl or vIL-10. Transplantation 59(6): 809–816, 1995.PubMedGoogle Scholar
  87. 87.
    Qin L, Ding Y, Bromberg JS. Gene transfer of transforming growth factor-ßl prolongs murine cardiac allograft survival by inhibiting cell mediated immunity. Hum Gene Ther 7(16): 1981–1988, 1996.PubMedCrossRefGoogle Scholar
  88. 88.
    Qin L, Ding Y, Pahud DR, Robson ND, Shaked A, Bromberg JS. Adenovirus-mediated gene transfer of viral interleukin-10 inhibits the immune response to both alloantigen and adenoviral antigen. Hum Gen Ther 8(11): 1365–1374, 1997a.CrossRefGoogle Scholar
  89. 89.
    Qin L, Ding Y, Pahud DR, Chang E, Imperiale MJ, Bromberg JS. Promoter attenuation in gene therapy: interferon-gamma and tumor necrosis factor-alpha inhibit transgene expression. Hum Gene Ther. 8(17):2019–2029, 1997b.PubMedCrossRefGoogle Scholar
  90. 90.
    Raper SE. Hepatocyte transplantation and gene therapy. Clin Transplantation. 9(3 Pt2):249–254, 1995.Google Scholar
  91. 91.
    Roman M, Martin-Orozco E, Goodman JS, Nguyen MD, Sato Y, Ronaghy A, Kornbluth RS, Richman DD, Carson DA, Raz E. Immunostimulatory DNA sequences function as T helper-l-promoting adjuvants [see comments]. Nat Med. 3(8):849–854, 1997.PubMedCrossRefGoogle Scholar
  92. 92.
    Rosenfeld MA, Siegfried W, Yoshimura K, Yoneyama K, Fukayama M, Stier LE, Paakko PK, Gilardi P, Stratford-Perricaudet LD, Perricaudet M, et al. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science. 252(5004):431–434, 1991.PubMedCrossRefGoogle Scholar
  93. 93.
    Rosenthal FM, Fruh R, Henschler R, Veelken H, Kulmburg P, Mackensen A, Gansbacher B, Mertelsmann R, Lindemannn A. Cytokine therapy with gene-transfected cells: Single injection of irradiated granulocyte-macrophage colony-stimulating factor-transduced cells accelerates hematopoietic recovery after cytotoxic chemotherapy in mice. Blood 84(9): 2960–2965, 1994.PubMedGoogle Scholar
  94. 94.
    Rousset F, Garcia E, Defrance T, Peronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereay J. Interleukin-10 is a potent growth hand differentiation factor for activated human B lymphocytes. Proc Natl Acad Sei USA 89(5): 1890–1893, 1992.CrossRefGoogle Scholar
  95. 95.
    (12), Zhu X., Xiao X,. Brook JD, Housman DE, Epstein N, Hunter LA. Targeted integration of adeno-associated virus (AAV) into human chromosome 19 [published erratum appears in EMBO J 11:1228, 1992] EMBO J. 10(12):3941–3950, 1991.PubMedGoogle Scholar
  96. 96.
    Sebestyen MG, Ludtke JJ, Bassik MC, Zhang G, Budker V, Lukhtanov EA., Hagstrom JE., Wolff JA. DNA vector chemistry: the covalent attachment of signal peptides to plasmid DNA. Nat Biotech. 16(1):80–85, 1998.CrossRefGoogle Scholar
  97. 97.
    Serup P, Jensen J, Andersen FG, Jaergensen MC, Blume N, Hoist JJ, Madsen OD. Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor I. Proc Natl Acad Sci USA 93(17):9015–9020, 1996.PubMedCrossRefGoogle Scholar
  98. 98.
    Shaked A, Csete ME, Drazan KE, Bullington D, WU L, Busuttil RW, Berk AJ. Adenovirus-mediated gene transfer in the transplant setting. II. Successful expression of transferred cDNA in syngeneic liver grafts. Transplantation 57(10):1508–1511, 1994.PubMedGoogle Scholar
  99. 99.
    Smith CV, Nakajima K, Mixon A, Guzetta PC, Rosengard BR, Fishbein JM, Sachs DH. Successful induction of long-term specific tolerance to fully allogeneic renal allografts in miniature swine. Transplantation 53(2):438–444. 1992.PubMedCrossRefGoogle Scholar
  100. 100.
    Soares MP, Muniappan A, Kaczmarek E, Koziak K, Wrighton CJ, Steinhauslin F, Ferran C, Winkler H, Bach FH, Anrather J. Adenovirus-mediated expression of a dominant negative mutant of p65/RelA inhibits proinflammatory gene expression in endothelial cells without sensitizing to apoptosis. J. Immunol. 161(9):4572–4582, 1998.PubMedGoogle Scholar
  101. 101.
    Spencer HT, Sleep SE, Rehg JE, Blakley RL, Sorrentino BP. A gene transfer strategy for making bone marrow cells resistant to trimetrexate. Blood 87(6):2579–2587, 1996.PubMedGoogle Scholar
  102. 102.
    Sun S, Zhang X, Tough DF, Sprent J. Type I interferon-mediated stimulation of T cells by CpG DNA. J. Expt Med. 188(12):2335–2342, 1998.CrossRefGoogle Scholar
  103. 103.
    Suzuki M, Singh R, Moore MA, Song WR, Crystal RG. Similarity of strain-and route-dependent murine responses to an adenovirus vector using the homologous thrombopoietin cDNA as the reporter genes. Hum Gene Ther. 9(8):1223–1231, 1998.PubMedCrossRefGoogle Scholar
  104. 104.
    Suzuki T, Tahara H, Narula S, Moore KW, Robbins PD, Lotze MT. Viral interleukin-10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors. J Exp Med 182(2):477–486, 1995.PubMedCrossRefGoogle Scholar
  105. 105.
    Suzuki T, Shin BC, Fujikura K, Matsuzaki T, Takata K. Direct gene transfer into rat liver cells by in vivo electroporation. FEBS Letters 425(3):436–440, 1998.PubMedCrossRefGoogle Scholar
  106. 106.
    Sykes M, Sachs DH, Nienhuis AW, Pearson DA, Moulton AD, Bodine DM. Specific prolongation of skin graft survival following retroviral transduction of bone marrow with an allogeneic major histocompatibility complex gene. Transplantation. 55(1): 197–202, 1993.PubMedCrossRefGoogle Scholar
  107. 107.
    Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 5(4):434–438, 1999.PubMedCrossRefGoogle Scholar
  108. 108.
    Thomas LH, Friedland JS, Sharland M, Becker S. Respiratory syncytial virus-induced RANTES production from human bronchial epithelial cells is dependent on nuclear factor-kappa B nuclear binding and is inhibited by adenovirus-mediated expression of inhibitor of kappa B alpha. J. Immunol. 161(2): 1007–1016, 1998.PubMedGoogle Scholar
  109. 109.
    Thompson-Snipes L, Dhar V, Bond MW, Mosmann TR, Moore KW, Rennick DM. Interleukin-10: a novel stimulatory factor for mast cells and their progenitors. J Exp Med 173(2):507–510, 1991.PubMedCrossRefGoogle Scholar
  110. 110.
    Tripathy SK, Black HB, Goldwasser E, Leiden JM. Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat Med. 2(5):545–550, 1996.PubMedCrossRefGoogle Scholar
  111. 111.
    Vieira P, de Waal Malefyt R, Dang MN, Johnson KE, Kastelein R, Fiorentino DF, de Vries JE, Roncarolo MG, Mosmann TR, and Moore KW. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci USA 88(4):1172–1176, 1991.PubMedCrossRefGoogle Scholar
  112. 112.
    Vinn DB, Mclvor RS. Selective expression of methotrexate-resistant dihydrofolate reductase (DHFR) activity in mice transduced with DHFR retrovirus and administered methotrexate. J Pharmacol Exp Ther 267(2):989–996, 1993.Google Scholar
  113. 113.
    Wadsworth SC, Zhou H, Smith AE, Kaplan JM. Adenovirus vector-infected cells can escape adenovirus antigen-specific cytotoxic T-lymphocyte killing in vivo. J. Virol. 71(7):5189–5196, 1997.PubMedGoogle Scholar
  114. 114.
    Weiner GJ., Liu HM, Wooldridge JE, Dahle CE, Krieg AM. Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization. Proc Nal Acad Sci USA. 94(20): 10833–10837, 1997.CrossRefGoogle Scholar
  115. 115.
    Welsh M, Welsh N, Nilsson T, Arkhammar P, Pepinsky RB, Steiner DF, Berggren P-O. Stimulation of pancreatic islet beta-cell replication by oncogenes. Proc Natl Acad Sci USA 85(1): 116–120, 1988.PubMedCrossRefGoogle Scholar
  116. 116.
    Wilson JM, Johnston DE, Jefferson DM, Mulligan RC. Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA. 85:4421–4425, 1988.PubMedCrossRefGoogle Scholar
  117. 117.
    Wolff JA, Malone RW, Williams P, Chang W, Ascadi G, Jani A, Feigner PL. Direct gene transfer into mouse muscle in vivo. Science 247(4949 Pt 1): 1465–1468, 1990.PubMedCrossRefGoogle Scholar
  118. 118.
    Worgall S, Leopold PL, Wolff G, Ferris B, Van Roijen N, Crystal RG. Role of alveolar macrophages in rapid elimination of adenovirus vectors administered to the epithelial surface of the respiratory tract. Hum Gene Ther. 8(14): 1675–1684, 1997a.PubMedCrossRefGoogle Scholar
  119. 119.
    Worgall S, Wolff G, Falck-Pedersen E, Crystal RG. Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration. Hum Gene Ther. 8(1): 37–44, 1997b.PubMedCrossRefGoogle Scholar
  120. 120.
    Wu GY, Wu CH. Receptor-mediated in vitro gene transformation by a soluble DNA carrier system, [published erratum appears in J Biol Chem. 263:588, 1988]. J BiolChem. 262(10):4429–4432, 1987.Google Scholar
  121. 121.
    Yamamoto S, Kuramoto E, Shimada S, Tokunaga T. In vitro augmentation of natural killer cell activity and production of interferon-alpha/beta and-gamma with deoxyribonucleic acid fraction from Mycobacterium bovis BCG. Japanese J. Can Res. 79(7):866–873, 1988.CrossRefGoogle Scholar
  122. 122.
    Yang Y, Ertl HC, Wilson JM. MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with El-deleted recombinant adenoviruses. Immunity. 1(5):433–442, 1994a.PubMedCrossRefGoogle Scholar
  123. 123.
    Yang Y, Nunes FA, Berencsi K, Furth EE, Gonczol E, Wilson JM. Cellular immunity to viral antigens limits El-deleted adenoviruses for gene therapy. Proc. Natl Acad Sei USA. 91(10):4407–4411, 1994b.CrossRefGoogle Scholar
  124. 124.
    Ye X, Rivera VM, Zoltick P, et al. Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer. Science. 283(5398):88–91, 1999.PubMedCrossRefGoogle Scholar
  125. 125.
    Yei S, Mittereder N, Wert S, Whitsett JA, Wilmott RW, Trapnell BC In vivo evaluation of the safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lung. Hum Gene Ther. 5(6):731–744, 1994.PubMedCrossRefGoogle Scholar
  126. 126.
    Yi AK, Chace JH, Cowdery JS, Krieg AM. IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides. J. Immunol. 156(2):558–564, 1996.PubMedGoogle Scholar
  127. 127.
    Yi AK, Tuetken R, Redford T, Waldschmidt M, Kirsch J, Krieg AM. CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. J. Immunol. 160(10):4755–4761, 1998a.PubMedGoogle Scholar
  128. 128.
    Yi AK, Krieg AM. CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation of I kappa B alpha and I kappa B beta and sustained activation of nuclear factor-kappa B/c-Rel. J. Immunol. 160(3): 1240–1245, 1998b.PubMedGoogle Scholar
  129. 129.
    Yi AK, Krieg AM. Rapid induction of mitogen-activated protein kinases by immune stimulatory CpG DNA. J. Immunol. 161(9):4493–4497, 1998c.PubMedGoogle Scholar
  130. 130.
    Zanta MA., Belguise-Valladier P, Behr JP. Gene delivery: a single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus. Proc Natl Acad Sei USA. 96(1):91–96, 1999.CrossRefGoogle Scholar
  131. 131.
    Zhong L, Granelli-Piperno A, Choi Y, Steinman RM. Recombinant adenovirus is an efficient and non-perturbing genetic vector for human dendritic cells. Eur J Immunol. 29(3):964–972, 1999.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • John C. Magee
  • Randall S. Sung
  • Jonathan S. Bromberg

There are no affiliations available

Personalised recommendations