Is there a Role for Transfusion Medicine in the Genetic Correction of Genetic Disorders and other Diseases?

  • J. A. Zwiebel
Part of the Developments in Hematology and Immunology book series (DIHI, volume 30)


Initially viewed principally as a means of treating inherited genetic diseases, gene therapy is now seen as a promising approach for virtually all kinds of disorders, and by disciplines as diverse as oncology, cardiology, endocrinology, and infectious diseases [1, 2]. There has been a rapid growth in the number of clinical trials that utilize gene transfer either for cell marking or therapeutic intent. While the usefulness of the gene transfer for patient care is not yet known, what is emerging is a profusion of different strategies and applications of clinical gene transfer. Its potential impact likened to that of the introduction of antibiotics, gene therapy may very well become part of the standard armamentarium of all clinicians. If gene therapy succeeds in realizing even part of its promise, there will be a need in medical institutions for a facility that can dispense the agents to be administered to patients in a gene therapy procedure. The transfusion laboratory, with its well-establishedrole for the collection, processing and distribution of cells and other blood components, is well-suited to serving this need.


Gene Therapy Gene Transfer Adenosine Deaminase Purine Nucleoside Phosphorylase Leukocyte Adhesion Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Miller AD. Human gene therapy comes of age. Nature 1992;357:455–69.PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson WF. Human gene therapy. Science 1992;256:808–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Mulligan RC. The basic science of gene therapy. Science 1993;260:926–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Curiel DT, Agarwal S, Rimer MU, et al. gene transfer to respiratory epithelial cells via the receptor-mediated endocytosis pathway. Am J Respir Cell Mol Biol 1992;6:247–52.PubMedGoogle Scholar
  5. 5.
    Weiss RA, Teich N, Varmus HE, Coffin J (eds). Molecular biology of tumor viruses: RNA tumor viruses Vol. 1 & Vol 2, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory 1985.Google Scholar
  6. 6.
    Stratford-Perricaudet LD, Levrero M, Chasse JF, Perricaudet M, Briand P. Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector. Hum Gene Ther 1990;1:241–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Wang Q, Konan V, Taylor MW. Expression of the APRT gene in an adenovirus vector system as a model for studying gene therapy. Adv Exp Med Biol 1991;309B:61–66.PubMedCrossRefGoogle Scholar
  8. 8.
    Rosenfeld MA, Siegfried W, Yoshimura K, et al. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo [see comments]. Science 1991;252:431–34.PubMedCrossRefGoogle Scholar
  9. 9.
    Mastrangeli A, Danel C, Rosenfeld MA, et al. Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer. J Clin Invest 1993; 91:225–34.PubMedCrossRefGoogle Scholar
  10. 10.
    Ragot T, Vincent N, Chafey P, et al. Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. Nature 1993;361:647–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Quantin B, Perricaudet LD, Tajbakhsh S, Mandel JL. Adenovirus as an expression vector in muscle cells in vivo. Proc Natl Acad Sci USA 1992;89:2581–84.PubMedCrossRefGoogle Scholar
  12. 12.
    Samulski RJ, Zhu X, Xiao X, et al. Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J 1991;10:3941–50.PubMedGoogle Scholar
  13. 13.
    Kotin RM, Siniscalco M, Samulski RJ, et al. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 1990;87:2211–15.PubMedCrossRefGoogle Scholar
  14. 14.
    Muzyczka N. Use of adeno-associated virus as a general transduction vector for mammalian cells. Curr Top Microbiol Immunol 1992;158:97–129.PubMedCrossRefGoogle Scholar
  15. 15.
    Dixit M, Webb MS, Smart WC, Ohi S. Construction and expression of a recombinant adeno-associated virus that harbors a human beta-globin-encoding cDNA. Gene 1991; 104:253–57.PubMedCrossRefGoogle Scholar
  16. 16.
    Flotte TR, Solow R, Owens RA, Afione S, Zeitlin PL, Carter BJ. Gene expression from adeno-associated virus vectors in airway epithelial cells. Am J Respir Cell Mol Biol 1992;7:349–56.PubMedGoogle Scholar
  17. 17.
    Huang Q, VonSattel JP, Schaffer PA, Martuza RL, Breakefield XO, DiFiglia M. Introduction of a foreign gene (Escherichia coli lacZ) into rat neostriatal neurons using herpes simplex virus mutants: A light and electron microscopic study. Exp Neurol 1992;115:303–16.PubMedCrossRefGoogle Scholar
  18. 18.
    Andersen JK, Garber DA, Meaney CA, Breakefiel XO. Gene transfer into mammalian central nervous system using herpes virus vectors: Extended expression of bacterial lacZ in neurons using the neuron-specific enolase promoter. Hum Gene Ther 1992; 3:487–99.PubMedCrossRefGoogle Scholar
  19. 19.
    Zenke M, Steinlein P, Wagner E, Cotten M, Beug H, Birnstiel ML. Receptor-mediated endocytosis of transferrin-polycation conjugates: An efficient way to introduce DNA into hematopoietic cells. Proc Natl Acad Sci USA 1990;87:3655–59.PubMedCrossRefGoogle Scholar
  20. 20.
    Dinur T, Schuchman EH, Fibach E, et al. Toward gene therapy for Niemann-Pick disease (NPD): Separation of retrovirally corrected and noncorrected NPD fibroblasts using a novel fluorescent sphingomyelin. Hum Gene Ther 1992;3:633–39.PubMedCrossRefGoogle Scholar
  21. 21.
    Uitto J, Christiano AM. Molecular genetics of the cutaneous basement membrane zone. Perspectives on epidermolysis bullosa and other blistering skin diseases. J Clin Invest 1992;90:687–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Albert N, Tremblay JP. Evaluation of various gene transfection methods into human myoblast clones. Transplant Proc 1992;24:2784–86.PubMedGoogle Scholar
  23. 23.
    Nabel EG, Yang Z, Liptay S, et al. Recombinant platelet-derived growth factor B gene expression in porcine arteries induce intimal hyperplasia in vivo. J Clin Invest 1993;91:1822–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Nabel EG, Gordon D, Yang ZY, et al. Gene transfer in vivo with DNA-liposome complexes: Lack of autoimmunity and gonadal localization. Hum Gene Ther 1992; 3:649–56.PubMedCrossRefGoogle Scholar
  25. 25.
    Hyde SC, Gill DR, Higgins CF, et al. Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy. Nature 1993;362:250–55.PubMedCrossRefGoogle Scholar
  26. 26.
    Nabel GJ. Principal investigator. Immunotherapy of malignancy by in vivo gene transfer into tumors. Hum Gene Ther 1992;3:399–410.CrossRefGoogle Scholar
  27. 27.
    Karlsson S. Treatment of genetic defects in hematopoietic cell function by gene transfer. Blood 1991;78:2481–92.PubMedGoogle Scholar
  28. 28.
    Eglitis MA, Kantoff P, Gilboa E, Anderson WF. Gene expression in mice after high efficiency retroviral-mediated gene transfer. Science 1985;230:1395–98.PubMedCrossRefGoogle Scholar
  29. 29.
    Williams DA, Lemischka IR, Nathan DG, Mulligan RC. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature 1984;310: 476–80.PubMedCrossRefGoogle Scholar
  30. 30.
    Belmont JW, Henkel-Tigges J, Chang SM, et al. Expression of human adenosine deaminase in murine haematopoietic progenitor cells following retroviral transfer. Nature 1986;322(6077):385–87.PubMedCrossRefGoogle Scholar
  31. 31.
    Dick JE, Magli MC, Huszar D, Philips RA, Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long term culture reconstitution of the hematopoietic system of W/Wv mice. Cell 1985;42:71–79.PubMedCrossRefGoogle Scholar
  32. 32.
    Wolfe JH, Sands MS, Barker JE, et al. Reversal of pathology in murine mycopolysac-charidosis type VII by somatic cell gene transfer. Nature 1992;360:749–53.PubMedCrossRefGoogle Scholar
  33. 33.
    Einerhand MP, Bakx TA, Kukler A, Valerio D. Factor affecting the transduction of pluripotent hematopoietic stem cells: Long-term expression of a human adenosine deaminase gene in mice. Blood 1993;81:254–63.PubMedGoogle Scholar
  34. 34.
    Kantoff PW, Gillio AP, McLachlin JR, et al. Expression of human adenosine deaminase in nonhuman promates after retrovirus-mediated gene transfer. J Exp Med 1987;166:219–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Bordignon C, Yu SF, Smith CA, et al. Retroviral vector-mediated high-efficiency expression of adenosine deaminase (AD) in hematopoietic long-term cultures of ADA-deficient marrow cells. Proc Natl Acad Sci USA 1989;86:6748–52.PubMedCrossRefGoogle Scholar
  36. 36.
    Van Beusechem VW, Kukler A, Heidt PJ, Valerio D. Long-term expression of human adenosine deaminase in rhesus monkeys transplanted with retrovirus-infected bone-marrow cells. Proc Natl Acad Sci USA 1992;89:7640–44.PubMedCrossRefGoogle Scholar
  37. 37.
    Bodine DM, Moritz T, Donahue RE, et al. Long-term in vivo expression of a murine adenosine deaminase gene in rhesus monkey hematopoietic cells of multiple lineages after retroviral mediated gene transfer into CD34+ bone marrow cells. Blood 1993; 82:1975–80.PubMedGoogle Scholar
  38. 38.
    Molta JA, Crooks GM, Overell RW, Williams DE, Kohn DB. Retroviral vector-mediated gene transfer into primitive human hematopoietic progenitor cells: Effects of mast cell growth factor (MGF) combined with other cytokines. Exp Hematol 1992; 20:1065–71.Google Scholar
  39. 39.
    Donahue RE, Kessler SW, Bodine DM, et al. In vivo evaluation of gene transfer to priate CD34+ cells. J Cellular Biochem 1992;16F:46.Google Scholar
  40. 40.
    Berenson RJ, Bensinger WI, Hill RS, et al. Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. Blood 1991;77:1717–22.PubMedGoogle Scholar
  41. 41.
    Hoogerbrugge PM, Vossen JM, Van Beusechem VW, Valerio D. Treatment of patients with severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency by autologous transplantation of genetically modified bone marrow cells. Hum Gene Ther 1992;3:553–58.PubMedCrossRefGoogle Scholar
  42. 42.
    Ekhterae D, Crumbleholme T, Karson E, Harrison MR, Anderson WF, Zanjani ED. Retroviral vector-mediated transfer of the bacterial neomycin resistance gene into fetal and adult sheep and human hematopoietic progenitors in vitro. Blood 1990;75:365–69.PubMedGoogle Scholar
  43. 43.
    Michejda M, Catz CS. Fetal therapy 1994. Fetal Diagn Ther 1994;9:209–12.PubMedCrossRefGoogle Scholar
  44. 44.
    Luks FI, Deprest JA, Vandenberghe K, Brosens IA, Lerut T. A model for fetal surgery through intrauterine endoscopy. J Pediatr Surg 1994;29:1007–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Morecki S, Karson E, Cornetta K, et al. Retrovirus-mediated gene transfer into CD4+ and CD8+ human T cell subsets derived from tumor-infiltrating lymphocytes and peripheral blood mononuclear cells. Cancer Immunol Immunother 1991;32:342–52.PubMedCrossRefGoogle Scholar
  46. 46.
    Kantoff PW, Kohn DB, Mitsuya H, et al. Correction of adenosine deaminase deficiency in cultured human T and B cell by retrovirus-mediated gene transfer. Proc Natl Acad Sci USA 1986;83:6563–67.PubMedCrossRefGoogle Scholar
  47. 47.
    Palmer TD, Thompson AR, Miller AD. Production of human factor IX in animals by genetically modified skin fibroblasts: Potential therapy for hemophilia B. Blood 1989;73:438–45.PubMedGoogle Scholar
  48. 48.
    St. Louis DA, Verma IM. An alternative approach to somatic cell gene therapy. Proc Natl Acad Sci USA 1988;85:3150–54.CrossRefGoogle Scholar
  49. 49.
    Dichek DA, Bratthauer GL, Beg ZH, et al. Retroviral vector mediated in vivo expression of low density lipoprotein receptors in the Watanabe heritable hyperlipidemic rabbit. Somatic Cell Mol Genet 1991;17:287–301.CrossRefGoogle Scholar
  50. 50.
    Palmer TD, Rosman GJ, Osborne WRA, Miller AD. Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci USA 1991;88:1330–34.PubMedCrossRefGoogle Scholar
  51. 51.
    Rosenberg MB, Friedmann T, Robertson RC, et al. Grafting genetically modified cells to the damaged brain: Restorative effects of NGF expression. Science 1988;242:1575–78.PubMedCrossRefGoogle Scholar
  52. 52.
    Scharfmann R, Axelrod JH, Verma IM. Long-term in vivo expression of retrovirus-mediated gene transfer in mouse fibroblast implants. Proc Natl Acad Sci USA 1991;88: 4626–30.PubMedCrossRefGoogle Scholar
  53. 53.
    Suchi M, Dinur T, Desnick RJ, et al. Retroviral-mediated transfer of the human acid sphingomyelinase cDNA: Correction of the metabolic defect in cultured Niemann-Pick disease cells. Proc Natl Acad Sci USA 1992;89:3227–31.PubMedCrossRefGoogle Scholar
  54. 54.
    Wilkemeyer M, Stankovics J, Foy T, Ledley FD. Propionate metabolism in cultured human cells after overexpression of recombinant methylmalonyl CoA mutase: Implications for somatic gene therapy. Somat Cell Mol Genet 1992;18:493–505.PubMedCrossRefGoogle Scholar
  55. 55.
    Occhiodoro T, Hopwood JJ, Morris CP, Anson DS. Correction of alpha-L-fucosidase deficiency in fucosidosis fibroblasts by retroviral vector-mediated gene transfer. Hum Gen Ther 1992;3:365–69.CrossRefGoogle Scholar
  56. 56.
    Wilson JM, Grossman M, Thompson AR, et al. Somatic gene transfer in the development of an animal model for primary hyperparathyroidism. Endocrinology 1992; 130:2947–54.PubMedCrossRefGoogle Scholar
  57. 57.
    Chowdhury JR, Grossman M, Gupta S, Chowdhury NR, Baker JR Jr, Wilson JM. Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits. Science 1991;254:1802–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Grossman M, Raper SE, Kozarsky K, et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolemia. Nat Genet 1994;6:335–41.PubMedCrossRefGoogle Scholar
  59. 59.
    Peng H, Armentano D, MacKenzie-Graham L, et al. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes. Proc Natl Acad Sci USA 1988;85:8146–50.PubMedCrossRefGoogle Scholar
  60. 60.
    Kay MA, Li Q, Liu TH, et al. Hepatic gene therapy: Persistent expression of human alpha 1-antitrypsin in mice after direct gene delivery in vivo. Hum Gene Ther 1992; 3:641–47.PubMedCrossRefGoogle Scholar
  61. 61.
    Armentano D, Thompson AR, Darlington G, Woo SLC. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: Potential for gene therapy of hemophilia B. Proc Natl Acad Sci USA 1990;87:6141–45.PubMedCrossRefGoogle Scholar
  62. 62.
    Engelhardt JF, Allen ED, Wilson JM. Reconstitution of tracheal grafts with a genetically modified epithelium. Proc Natl Acad Sci USA 1991;88:11192–96.PubMedCrossRefGoogle Scholar
  63. 63.
    Yoshimura K, Rosenfeld MA, Nakamura H, et al. Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid-mediated gene transfer. Nucleic Acids Res 1992;20:3233–40.PubMedCrossRefGoogle Scholar
  64. 64.
    Engelhardt JF, Yankaskas JR, Wilson JM. In vivo retroviral gene transfer into human bronchial epithelia of xenografts. J Clin Invest 1992;90:2598–607.PubMedCrossRefGoogle Scholar
  65. 65.
    Nabel EG, Plautz G, Nabel GJ. Gene transfer into vascular cells. J Am Coll Cardiol 1991;17:189B–94B.PubMedCrossRefGoogle Scholar
  66. 66.
    Zwiebel JA, Freeman SM, Kantoff PW, Cornetta K, Ryan US, Anderson WF. High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors. Science 1989;243:220–22.PubMedCrossRefGoogle Scholar
  67. 67.
    Dichek DA, Neville RF, Zwiebel JA, Freeman SM, Leon MB, Anderson WF. Seeding of intravascular stents with genetically engineered endothelial cells [see comments]. Circulation 1989;80:1347–53.PubMedCrossRefGoogle Scholar
  68. 68.
    Dichek DA, Nussbaum O, Degen SJ, Anderson WF. Enhandement of the fibrinolytic activity of sheep endothelial cells by retroviral vector-mediated gene transfer. Blood 1991;77:533–41.PubMedGoogle Scholar
  69. 69.
    Yao SN, Wilson JM, Nabel EG, Kurachi S, Hachiya HL, Kurachi K. Expression of human factor IX in rat capillary endothelial cells: Toward somatic gene therapy for hemophilia B. Proc Natl Acad Sci USA 1991;88:8101–5.PubMedCrossRefGoogle Scholar
  70. 70.
    Nabel EG, Plautz G, Boyce FM, Stanley JC, Nabel GJ. Recombinant gene expression in vivo within endothelial cells of the arterial wall. Science 1989;244:1342–44.PubMedCrossRefGoogle Scholar
  71. 71.
    Nabel EG, Plautz G, Nabel GJ. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science 1990;249:1285–88.PubMedCrossRefGoogle Scholar
  72. 72.
    Lim CS, Chapman GD, Gammon RS, et al. Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog [see comments]. Circulation 1991;83: 2007–11.PubMedCrossRefGoogle Scholar
  73. 73.
    Lynch CM, Clowes MM, Osborne WR, Clowes AW, Miller AD. Long-term expression of human adenosine deaminase in vascular smooth muscle cells of rats: A model for gene therapy. Proc Natl Acad Sci USA 1992;89:1138–42.PubMedCrossRefGoogle Scholar
  74. 74.
    Thompson JA, Anderson KD, DiPietro JM, et al. Sit-directed neovessel formation in vivo. Science 1988;241:1349–52.PubMedCrossRefGoogle Scholar
  75. 75.
    Ojeifo JO, Forough R, Maciag T, Zwiebel J. Genetically-modified endothelial cells administered intravenously are incorporated into sites of active angiogenesis. J Cell Biochem 1992;Suppl 16F:50.Google Scholar
  76. 76.
    Thompson JA, Haudenschild CC, Anderson KD, DiPietro JM, Anderson WF, Maciag T. Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo [published erratum appears in Proc Natl Acad Sci USA90 1990 Feb;87(4):1625]. Proc Natl Acad Sci USA 1989;86:7928–32.PubMedCrossRefGoogle Scholar
  77. 77.
    Dickson G, Love DR, Davies KE, Wells KE, Piper TA, Walsh FS. Human dystrophin gene transfer: Production and expression of a functional recombinant DNA-based gene. Hum Genet 1991;88:53–58.PubMedCrossRefGoogle Scholar
  78. 78.
    Hughes SM, Blau HM. Muscle fiber pattern is independent of cell lineage in postnatal rodent development. Cell 1992;68:659–71.PubMedCrossRefGoogle Scholar
  79. 79.
    Barr E, Leiden JM. Systemic delivery of recombinant proteins by genetically modified myoblasts [see comments]. Science 1991;254:1507–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Dhawan J, Pan LC, Pavlath GK, Travis MA, Lanctot AM, Blau HM. Systemic delivery of human growth hormone by injection of genetically engineered myoblasts [see comments]. Science 1991;254:1509–12.PubMedCrossRefGoogle Scholar
  81. 81.
    Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse muscle in vivo. Science 1990;247:1465–68.PubMedCrossRefGoogle Scholar
  82. 82.
    Short MP, Choi BC, Lee JK, Malick A, Breakefield XO, Martuza RL. Gene delivery to glioma cells in rat brain by grafting of a retrovirus packaging cell line. J Neurosci Res 1990;27:427–39.PubMedCrossRefGoogle Scholar
  83. 83.
    Geller AI, Keyomarsi K, Bryan J, Pardee AB. An efficient deletion mutant packaging system for defective herpes simplex virus vectors: Potential applications to human gene therapy and neuronal physiology. Proc Natl Acad Sci USA 1990;87:8950–54.PubMedCrossRefGoogle Scholar
  84. 84.
    Sanes JR, Rubinstein J-LR, Nicolas J-F. The use of recombinant retrovirus to study post-implantation cell lineage in mouse embryos. EMBO 1986;5:3133–42.Google Scholar
  85. 85.
    Price J, Turner D, Cepko C. Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer.Proc Natl Acad Sci USA 1987;84:156–60.PubMedCrossRefGoogle Scholar
  86. 86.
    Stocker KM, Brown AM, Ciment G, Gene transfer of lacZ into avian neural tube and neural crest cells by retroviral infection of grafted embryonic tissues. J Neurosci Res 1993;34:135–45.PubMedCrossRefGoogle Scholar
  87. 87.
    Zwiebel JA, Su N, MacPherson A, Davis T, Ojeifo JO. the gene therapy of cancer; Transgenic immunotherapy. Sem Hematol 1994;30:119–29.Google Scholar
  88. 88.
    Moolten FL, Wells JM, Heyman RA, Evans RM. Lymphoma regression induced by ganciclovir in mice bearing a herpes thymidine kinase transgen. Hum Gene Ther 1990; 1:125–34.PubMedCrossRefGoogle Scholar
  89. 89.
    Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst 1990;82:297–300.PubMedCrossRefGoogle Scholar
  90. 90.
    Freeman SM, Whartenby KA, Koeplin DS, Moolten FL, Abboud CN, Abraham GN. Tumor regression when a fraction of the tumor mass contains the HSV-TK gene. J Cell Biol 1992;16F:47.Google Scholar
  91. 91.
    Short MP, Choi BC, Lee JK, Malick A, Breakefield XO, Martuza RL. Gene delivery to glioma cells in rat brain by grafting of a retrovirus packaging cell line. J Neurosci Res 1990;27:427–39.PubMedCrossRefGoogle Scholar
  92. 92.
    Takamiya Y, Short MP, Ezzeddine ZD, Moolten FL, Breakefield XO, Martuza RL. Gene therapy of malignant brain tumors: A rat glioma line bearing the herpes simplex virus type 1-thymidine kinase gene and wild type retrovirus kills other tumor cells. J Neurosci Res 1992;33:493–503.PubMedCrossRefGoogle Scholar
  93. 93.
    Culver KW, Ram Z, Wallbridge S, Ishii H, Oldfield EH, Blaese RM. in vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors [see comments]. Science 1992;256:1550–52.PubMedCrossRefGoogle Scholar
  94. 94.
    Li CL, Dwarki VJ, Verma IM. Expression of human alpha-globin and mouse/human hybrid beta-globin genes in murine hemopoietic stem cells transduced by recombinant retroviruses. Proc Natl Acad Sci USA 1990;87:4349–53.PubMedCrossRefGoogle Scholar
  95. 95.
    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.PubMedCrossRefGoogle Scholar
  96. 96.
    Weber-Benarous A, Cone RD, London IM, Mulligan RC. Retroviral-mediated transfer and expression of human beta-globin genes in cultured murine and human erythroid cells. J Biol Chem 1988;263:6142–45.PubMedGoogle Scholar
  97. 97.
    Bender MA, Gelinas RE, Miller AD. A majority of mice show long-term expression of a human beta-globin gene after retrovirus transfer into hematopoietic stem cells. Mol Cell Biol 1989;9:1426–34.PubMedGoogle Scholar
  98. 98.
    Osborne WR, Miller AD. Design of vectors for efficient expression of human purine nucleoside Phosphorylase in skin fibroblasts from enzyme-deficient humans. Proc Natl Acad Sci USA 1988;85:6851–55.PubMedCrossRefGoogle Scholar
  99. 99.
    McIvor RS, Johnson MJ, Miller AD, et al. Human purine nucleoside Phosphorylase and adenosine deaminase: Gene transfer into cultured cells and murine hematopoietic stem cells by using recombinant amphotropic retroviruses. Mol Cell Biol 1987;7:838–46.PubMedGoogle Scholar
  100. 100.
    McIvor RS, Goddard JM, Simonsen CC, Martin DW Jr. Expression of a cDNA sequence encoding human purine nucleoside Phosphorylase in rodent and human cells. Mol Cell Biol 1985;5:1349–57.PubMedGoogle Scholar
  101. 101.
    Foresman MD, Nelson DM, McIvor RS. Correction of purine nucleoside Phosphorylase deficiency by retroviral-mediated gene transfer in mouse S49 T cell lymphoma: A model for gene therapy of T cell immunodeficiency. Hum Gene Ther 1992;3:625–31.PubMedCrossRefGoogle Scholar
  102. 102.
    Brinkhous KM, Reddick RL, Read MS, Nichols TC, Bellinger DA, Griggs TR. Von Willebrand factor and animal models: Contributions to gene therapy, thrombotic thrombocytopenic purpura, and coronary artery thrombosis. Mayo Clin Proc 1991;66: 73–42.Google Scholar
  103. 103.
    Kaufman RJ, Wasley LC, Davies MV, Wise RJ, Israel DI, Dorner AJ. Effect of von Willebrand factor coexpression on the synthesis and secretion of factor VIII in Chinese hamster ovary cells. Mol Cell Biol 1989;9:1233–42.PubMedGoogle Scholar
  104. 104.
    Dai Y, Roman M, Naviaux RK, Verma IM. Gene therapy via primary myoblasts: Long-term expression of factor IX protein following transplantation in vivo. Proc Natl Acad Sci USA 1992;89:10892–95.PubMedCrossRefGoogle Scholar
  105. 105.
    Brinkhous KM. Gene transfer in the hemophilias: Retrospect and prospect. Thromb Res 1992;67:329–38.PubMedCrossRefGoogle Scholar
  106. 106.
    Hoeben RC, Einerhand MP, Briët E, van Ormondt H, Valerio D, van der Eb AJ, Toward gene therapy in haemophilia A; Retrovirus-mediated transfer of a factor VIII gene into murine haematopoietic progenitor cells. Thromb Haemost 1992;67:341–45.PubMedGoogle Scholar
  107. 107.
    Grompe M, Mitani K, Lee CC, Jones SN, Caskey CT. Gene therapy in man and mice: Adenosine deaminase deficiency, ornithine transcarbamylase deficiency, and Duchenne muscular dystrophy. Adv Exp Med Biol 1991;309B:51–56.PubMedCrossRefGoogle Scholar
  108. 108.
    Dubowitz V. The muscular dystrophies. Postgrad Med J 1992;68:500–06.PubMedCrossRefGoogle Scholar
  109. 109.
    Shrager JB, Naji A, Kelly AM, Stedman HH. A PCR-based assay for the wild-type dystrophin gene transferred into the mdx mouse. Muscle Nerve 1992;15:1133–37.PubMedCrossRefGoogle Scholar
  110. 110.
    Chamberlain JS. X-linked dystrophies: From gene localization to gene therapy. Curr Opin Neurol Neurosurg 1992;5:610–14.PubMedGoogle Scholar
  111. 111.
    Wilson JM, Ping AJ, Krauss JC, et al. Correction of CD18-deficient lymphocytes by retrovirus-mediated gene transfer. Science 1990;248:1413–16.PubMedCrossRefGoogle Scholar
  112. 112.
    Krauss JC, Bond LM, Todd RF, Wilson JM. Expression of retroviral transduced human CD18 in murine cells: An in vivo model of gene therapy for leukocyte adhesion deficiency. Hum Gene Ther 1991;2:221–28.PubMedCrossRefGoogle Scholar
  113. 113.
    Krauss JC, Ping AJ, Mayo-Bond L, et al. Complementation of genetic and functional defects in CD18-deficient lymphocytes by retrovirus-mediated gene transfer. Trans Assoc Am Physicians 1990;103:263–70.PubMedGoogle Scholar
  114. 114.
    Thrasher A, Chetty M, Casimir C, Segal AW. Restoration of superoxide generation to a chronic granulomatous disease-derived B-cell line by retrovirus mediated gene transfer. Blood 1992;80:1125–29.PubMedGoogle Scholar
  115. 115.
    Cobbs CS, Malech HL, Leto TL, et al. Retroviral expression of recombinant p47phox protein by Epstein-Barr virus-transformed B lymphocytes from a patient with autosomal chronic granulomatous disease. Blood 1992;79:1829–35.PubMedGoogle Scholar
  116. 116.
    Leto TL, Lomax KJ, Volpp BD, et al. Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src. Science 1990;248:727–30.PubMedCrossRefGoogle Scholar
  117. 117.
    Wilson JM, Chowdhury JR. Prospects for gene therapy of familial hypercholesterolemia. Mol Biol Med 1990;7:223–32.PubMedGoogle Scholar
  118. 118.
    Wilson JM, Grossman M, Wu CH, Chowdhury NR, Wu GY, Chowdhury JR. Hepatocyte-directed gene transfer in vivo leads to transient improvement of hypercholesterolemia in low density lipoprotein receptor-deficient rabbits. J Biol Chem 1992; 267:963–67.PubMedGoogle Scholar
  119. 119.
    Wilson JM, Grossman M, Raper SE, Baker JR Jr, Newton RS, Thoene JG. Ex vivo gene therapy of familial hypercholesterolemia. Hum Gene Ther 1992;3:179–222.PubMedCrossRefGoogle Scholar
  120. 120.
    Grossman M, Wilson JM, Raper SE. A novel approach for introducing hepatocytes into the portal circulation. J Lab Clin Med 1993;121:472–78.PubMedGoogle Scholar
  121. 121.
    Garver RI Jr, Chytil A, Karlsson S, et al. Production of glycosylated physiologically “normal” human alpha 1-antitrypsin by mouse fibroblasts modified by insertion of a human alpha 1-antitrypsin cDNA using a retroviral vector. Proc Natl Acad Sci USA 1987;84:1050–54.PubMedCrossRefGoogle Scholar
  122. 122.
    Garver RI Jr, Chytil A, Courtney M, Crystal RG. Clonal gene therapy: in vivo expression of a transplanted monoclonal population of murine fibroblasts containing a retrovirus inserted human alpha 1 antitrypsin gene. Trans Assoc Am Physicians 1987; 100:10–20.PubMedGoogle Scholar
  123. 123.
    Garver RI Jr, Chytil A, Courtney M, Crystal RG. Clonal gene therapy: Transplanted mouse fibroblast clones express human alpha 1-antitrypsin gene in vivo. Science 1987; 237:762–64.PubMedCrossRefGoogle Scholar
  124. 124.
    Kay MA, Baley P, Rothenberg S, et al. Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. Proc Natl Acad Sci USA 1992;89:89–93.PubMedCrossRefGoogle Scholar
  125. 125.
    Crystal RG, Gene therapy strategies for pulmonary disease. Am J Med 1992;92:44S–52S.PubMedCrossRefGoogle Scholar
  126. 126.
    Grompe M, Jones SN, Loulseged H, Caskey CT. Retroviral-mediated gene transfer of human ornithine transcarbamylase into primary hepatocytes of spf and spf-ashmice. Hum Gene Ther 1992;3:35–44.PubMedCrossRefGoogle Scholar
  127. 127.
    Stankovics J, Ledley FD. Cloning of functional alpha propionyl CoA carboxylase and correction of enzyme deficiency in pccA fibroblasts. Am J Hum Genet 1993;52:144–51.PubMedGoogle Scholar
  128. 128.
    Sawada T, Ledley FD. Correction of methylmalonyl-CoA mutase deficiency in Mut0 fibroblasts and constitution of gene expression in primary human hepatocytes by retroviral-mediated gene transfer. Somat Cell Mol Genet 1992;18:507–16.PubMedCrossRefGoogle Scholar
  129. 129.
    Miller AD, Jolly DJ, Friedmann T, Verma IM. A transmissible retrovirus expressing human hypoxanthine phosphoribosytransferase (HPRT): Gene transfer into cells obtained from humans deficient in HPRT. Proc Natl Acad Sci USA 1983;80:4709–13.PubMedCrossRefGoogle Scholar
  130. 130.
    Willis RC, Jolly DJ, Miller AD, et al. partial phenotypic correction of human Lesch-Nyhan (hypoxanthine-guanine phosphoribosyltransferase-deficient) lymphoblasts with a transmissible retroviral vector. J Biol Chem 1984;259:7842–49.PubMedGoogle Scholar
  131. 131.
    Choudary PV, Barranger JA, Tsuji S, et al. Retrovirus-mediated transfer of the human glucocerebrosidase gene to Gaucher fibroblasts. Mol Biol Med 1986;3:293–99.PubMedGoogle Scholar
  132. 132.
    Sorge J, Kuhl W, West C, Beutler E. Complete correction of the enzymatic defect of type I Gaucher disease fibroblasts by retroviral-mediated gene transfer. Proc Natl Acad Sci USA 1987;84:906–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Kohn DB, Nolta JA, Weinthal J, et al. Toward gene therapy for Gaucher disease. Hum Gene Ther 1991;2:101–5.PubMedCrossRefGoogle Scholar
  134. 134.
    Molta JA, Yu XJ, Bahner I, Kohn DB. Retroviral-mediated transfer of the human glucocerebrosidase gene into cultured Gaucher bone marrow [published erratum appears in J Clin Invest 1992 Oct;90(4):following 1634]. J Clin Invest 1992;90:342–48.CrossRefGoogle Scholar
  135. 135.
    Zwiebel JA. Implants of genetically modified cells for gene therapy. In: Hackel E, Aubuchon J (eds). Advances in transplantation. Bethesda, MD: American Association of Blood Banks 1993:113–42.Google Scholar

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© Springer Science+Business Media Dordrecht 1995

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  • J. A. Zwiebel

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