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Molecular Neurobiology

, Volume 15, Issue 2, pp 241–256 | Cite as

Gene therapy for Parkinson's disease

  • Philippe Horellou
  • Jacques Mallet
Original Articles

Abstract

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. The discovery of neurotrophic factors inhibiting neurodegenerative processes and neurotransmitter-synthesizing enzymes provides the basis for current gene therapy strategies for Parkinson's disease. Genes can be transferred by viral or nonviral vectors. Of the various possible vectors, recombinant retroviruses are the most efficient for genetic modification of cells in vitro that can thereafter be used for transplantation (ex vivo gene therapy approach). Recently, in vivo gene transfer to the brain has been developed using adenovirus vectors. One of the advantages of recombinant adenovirus is that it can transduced both quiescent and actively dividing cells, thereby allowing both direct in vivo gene transfer and ex vivo gene transfer to neural cells. Probably because the brain is partially protected from the immune system, the expression of adenoviral vectors persists for several months with little inflammation. Novel therapeutic tools, such as vectors for gene therapy have to be evaluated in terms of efficacy and safety for future clinical trials. These vectors still need to be improved to allow long-term and possibly regulatable expression of the transgene.

Index Entries

Gene therapy recombinant adenovirus recombinant retrovirus glial cell line-derived neurotrophic factor tyrosine hydroxylase Parkinson's disease 

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References

  1. Akli S., Caillaud C., Vigne E., Stratford-Pierricaudet L. D., Poenaru L., Perricaudet M., Kahn A., and Peschanski M. (1993) Transfer of a foreign gene into the brain using adenovirus vectors.Nature Genet. 3, 224–228.PubMedCrossRefGoogle Scholar
  2. Anton R., Kordower J. H., Maidment N. T., Manaster J. S., Kane D. J., Rabizadeh S., Schueller S. B., Yang J., Rabizadeh S., Edwards R. H., Markham C. H., and Bredesen D. E. (1994) Neural-targeted gene therapy for rodent and primate hemiparkinsonism.Exp. Neurol. 127, 207–218.PubMedCrossRefGoogle Scholar
  3. Bajocchi G., Feldman S. H., Crystal R. G., and Mastrangeli A. (1993) Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors.Nature Genet. 3, 229–234.PubMedCrossRefGoogle Scholar
  4. Baltimore D. (1970) RNA-dependent DNA polymerase in virions of RNA tumour viruses.Nature 226, 1209–1211.PubMedCrossRefGoogle Scholar
  5. Beck K. D., Valverde J., Alexi T., Poulsen K., Moffat B., Vandlen R. A., Rosenthal A., and Hefti F. (1995) Mesencephalic dopaminergic neurons protected by GDNF from axotomyinduced degeneration in the adult brain.Nature 373, 339–341.PubMedCrossRefGoogle Scholar
  6. Bilang-Bleuel A., Revah F., Colin P., Locquet I., Robert J. J., Mallet J., and Horellou P. (1997) Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease.Proc. Natl. Acad. Sci. USA 94, 8818–8823.PubMedCrossRefGoogle Scholar
  7. Bjorklund A. and Stenevi U. (1979) Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants.Brain Res. 177, 555–560.PubMedCrossRefGoogle Scholar
  8. Bloom D. C., Maidment N. T., Tan A., Dissette V. B., Feldman L. T., and Stevens J. G. (1995) Longterm expression of a reporter gene from latent herpes simplex virus in the rat hippocampus.Mol. Brain Res. 31, 48–60.PubMedCrossRefGoogle Scholar
  9. Brundin P., Strecker R. E., Lindvall O., Isacson O., Nilsson O. G., Barbin G., Prochiantz A., Forni C., Nieoullon A., Widner H., Gage F. H., and Bjorklund A. (1987) Intracerebral grafting of dopamine neurons. Experimental basis for clinical trials in patients with parkinson's disease.Ann. NY Acad. Sci. 495, 473–496.PubMedCrossRefGoogle Scholar
  10. Buc-Caron M.-H. (1995) Neuroepithelial progenitor cells explanted from human fetal brain proliferate and differentiate in vitro.Neurobiol. Disease 2, 37–47.CrossRefGoogle Scholar
  11. Chen D. and Okayama H. (1987) High-efficiency transformation of mammalian cells by plasmid DNA.Mol. Cell. Biol. 7, 2745–2752.PubMedGoogle Scholar
  12. Choi-Lundberg D. L., Lin Q., Mohajeri H., Chang Y. N., Chiang Y. L., Hay C. M., Davidson B. L., and Bohn M. C. (1997) GDNF delivered via an adenoviral vector protects rat dopaminergic neurons from degeneration.Science 275, 838–841.PubMedCrossRefGoogle Scholar
  13. Colbere-Garapin F., Horodniceanu F., Kourilsky P., and Garapin A. C. (1981) A new dominant hybrid selective marker for higher eukaryotic cells.J. Mol. Biol. 150, 1–14.PubMedCrossRefGoogle Scholar
  14. Cone R. D., Weber-Benarous A., Baorto D., and Mulligan R. C. (1987) Regulated expression of a complete human β-globin gene encoded by a transmissible retrovirus vector.Mol. Cell. Biol. 7, 887–897.PubMedGoogle Scholar
  15. Cunningham L. A., Hansen J. T., Short M. P., and Bohn M. C. (1991) the use of genetically altered astrocytes to provide nerve growth factor to adrenal chromaffin cells grafted into the striatum.Brain Res. 561, 192–202.PubMedCrossRefGoogle Scholar
  16. Danos O. and Mulligan R. C. (1988) Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges.Proc. Natl. Acad. Sci. USA 85, 6460–6464.PubMedCrossRefGoogle Scholar
  17. Davidson B. L., Allen E. D., Kozarsky K. F., Wilson J. M., and Roessler B. J. (1993) A model system for in vivo gene transfer into the central nervous system using an adenoviral vector.Nature Genet. 3, 219–223.PubMedCrossRefGoogle Scholar
  18. Dougherty J. P. and Temin H. M. (1987) A promoterless retroviral vector indicates that there are sequences in U3 required for 3′ RNA processing.Proc. Natl. Acad. Sci. USA 84, 1197–1201.PubMedCrossRefGoogle Scholar
  19. During M. J., Naegele J. R., O'Malley K. L., and Geller A. I. (1994) Long-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase.Science 266, 1399–1403.PubMedCrossRefGoogle Scholar
  20. Emerman M. and Temin H. M. (1984) Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism.Cell 39, 449–467.PubMedCrossRefGoogle Scholar
  21. Emerman M. and Temin H. M. (1984) Highfrequency deletion in recovered retrovirus vectors containing exogenous DNA with promoters.J. Virol. 50, 42–49.PubMedGoogle Scholar
  22. Fink D. J., Sternberg L. R., Weber P. C., Mata M., Goins W. F., and Glorioso J. C. (1992) In vivo expression of β-galactosidase in hippocampual neurons by HSV-mediated gene transfer.Hum. Gene Ther. 3, 12–19.Google Scholar
  23. Fisher L. J., Jinnah H. A., Kale L. C., Higgins G. A., and Gage F. H. (1991) Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-Dopa.Neuron 6, 371–380.PubMedCrossRefGoogle Scholar
  24. Friedmann T. and Roblin R. (1972) Gene therapy for human genetic disease?Science 175, 949–955.PubMedCrossRefGoogle Scholar
  25. Ganem D., Nussbaum A. L., Davoli D., and Fareed G. C. (1976) Propagation of a segment of bacteriophage lambda-DNA in monkey cells after covalent linkage to a defective simian virus 40 genome.Cell 7, 349–359.PubMedCrossRefGoogle Scholar
  26. Gash D. M., Zhang Z., Ovadia A., Cass W. A., Yi A., Simmerman L., Russell D., Martin D., Lapchak P. A., Collins F., Hoffer B. J., and Gerhardt G. A. (1996) Functional recovery in GDNF-treated parkinsonian monkeys.Nature 380, 252–255.PubMedCrossRefGoogle Scholar
  27. Gilboa E., Goff S., Shields A., Yoshimura F., Mitra S., and Baltimore D. (1979) In vitro synthesis of a 9 kbp terminally redundant DNA carrying the infectivity of Moloney murine leukemia virus.Cell 16, 863–874.PubMedCrossRefGoogle Scholar
  28. Goff S. P. and Berg P. (1976) Construction of hybrid viruses containing SV40 and lambda phage DNA segments and their propagation in cultured monkey cells.Cell 9, 695–705.PubMedCrossRefGoogle Scholar
  29. Goldman M. J. and Wilson J. M. (1995) Expression of alpha v beta 5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway.J. Virol. 69, 5951–5958.PubMedGoogle Scholar
  30. Graham F. L., Smiley J., Russell W. C., and Nairn R. (1977) Characteristics of a human cell line transformed by DNA from human adenovirus 5.J. Gen. Virol. 36, 59–72.PubMedCrossRefGoogle Scholar
  31. Graham F. C. and van der Eb A. J. (1973) A new technique for the assay of infectivity of human adenovirus 5 DNA.Virology 52, 456–467.PubMedCrossRefGoogle Scholar
  32. Heidmann T., Heidmann O., and Nicolas J.-F. (1988) An indicator gene to demonstrate intracellular transposition of defective retroviruses.Proc. Natl. Acad. Sci. USA 89, 2219–2223.CrossRefGoogle Scholar
  33. Horellou P., Guibert B., Leviel V., and Mallet J. (1989) Retroviral transfer of a human tyrosine hydroxylase cDNA in various cell lines: regu-lated release of dopamine in mouse anterior pituitary AtT-20 cells.Proc. Natl. Acad. Sci. USA 86, 7233–7237.PubMedCrossRefGoogle Scholar
  34. Horellou P., Brundin P., Kalen P., Mallet J., and Bjorklund A. (1990a) In vivo release of DOPA and dopamine from genetically engineered cells grafted to the denervated rat striatum.Neuron 5, 393–402.PubMedCrossRefGoogle Scholar
  35. Horellou P., Marlier L., Privat A., and Mallet J. (1990b) Behavioural effect of engineered cells that synthesize L-DOPA or dopamine after grafting into the rat neostriatum.Eur. J. Neurosci. 2, 116–119.PubMedCrossRefGoogle Scholar
  36. Horellou P., Vigne E., Castel M. N., Barnéoud P., Colin P., Perricaudet M., Delaere P., and Mallet J. (1994) Direct intracerebral gene transfer of an adenoviral vector expressing tyrosine hydroxylase in a rat model of Parkinson's disease.Neuroreport 6, 49–53.PubMedCrossRefGoogle Scholar
  37. Hou J. G., Lin L. F., and Mytilineou C. (1996) Glial cell line-derived neurotrophic factor exerts neurotrophic effects on dopaminergic neurons in vitro and promotes their survival and regrowth after damage by 1-methyl-4-phenylpyridinium.J. Neurochem. 66, 74–82.PubMedCrossRefGoogle Scholar
  38. Huang S., Endo R. I., and Nemerow G. R. (1995) Upregulation of integrins alpha v beta 3 and alpha v beta 5 on human monocytes and 1 lymphocytes facilitates adenovirus-mediated gene delivery.J. Virol. 69, 2257–2263.PubMedGoogle Scholar
  39. Kaplitt M. G., Leone P., Samulski R. J., Xiao X., Pfaff D. W., O'Malley K. L., and During M. J. (1994) Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain.Nature Genet. 8, 148–154.PubMedCrossRefGoogle Scholar
  40. Kuehn M. R., Bradley A., Robertson E. J., and Evans M. J. (1987) A potential animal model for the human Lesch-Nyhan syndrome through introduction of HPRT mutations into mice.Nature 326, 295–298.PubMedCrossRefGoogle Scholar
  41. Le Gal La Salle G., Robert J. J., Berrard S., Ridoux V., Stratford-Perricaudet L. D., Perricaudet M., and Mallet J. (1993) An adenovirus vector for gene transfer into neurons and glia in the brain.Science 259, 988–990.PubMedCrossRefGoogle Scholar
  42. Lin L. F., Zhang T. J., Collins F., and Armes L. G. (1994) Purification and initial characterization of rat B49 glial cell line-derived neurotrophic factor.J. Neurochem. 63, 758–768.PubMedCrossRefGoogle Scholar
  43. Lin L. F., Doherty D. H., Lile J. D., Bektesh S., and Collins F. (1993) GDNF: a glial cell linederived neurotrophic factor for midbrain dopaminergic neurons.Science 260, 1130–1132.PubMedCrossRefGoogle Scholar
  44. Lindvall O., Sawle G., Widner H., Rothwell J. C., Bjorklund A., Brooks D., Brundin P., Frackowiak R., Marsden C. D., Odin P., et al. (1994) Evidence for long-term survival ancl function of dopaminergic grafts in progressive Parkinson's disease.Ann. Neurol. 35, 172–180.PubMedCrossRefGoogle Scholar
  45. Lindvall O., Brundin P., Widner H., Relmcrona S., Gustavii B., Frackowlak R., Leenders K. L., Sawle G., Rothwell J. C., Marsden C. D., and Bjorklund A. (1990) Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease.Science 247, 574–577.PubMedCrossRefGoogle Scholar
  46. Lundberg C., Horellou P., Mallet J., and Bjorklund A. (1996) Generation of DOPA-producing astrocytes by retroviral transduction of the human tyrosine hydroxylase gene: in vitro characterization and in vivo effects in the rat Parkinson model.Exp. Neurol. 139, 39–53.PubMedCrossRefGoogle Scholar
  47. Mallet J., Blanot F., Boni C., Dumas S., Faucon-Biguet N., Grima B., Horellou P., Julien J. F., Kahn P., Lamouroux A., et al. (1987) A molecularr genetic approach to the study of catecholamines.Biochem. Soc. Trans. 15, 126–128.PubMedGoogle Scholar
  48. Mann R., Mulligan R. C., and Baltimore D. (1983) Construction of a packaging mutant and its use to produce helper-free defective retrovirus.Cell 33, 153–159.PubMedCrossRefGoogle Scholar
  49. Markowitz D., Goff S., and Bank A. (1988) A safe packaging line for gene transfer: separating viral genes on two different plasmids.J. Virol. 62, 1120–1124.PubMedGoogle Scholar
  50. Marsden C. D. and Parkes J. D. (1976) “On-off” effects in patients with Parkinson's disease on chronic levodopa therapy.Lancet 1, 292–296.PubMedCrossRefGoogle Scholar
  51. Martin G. S. (1970) Rous sarcoma virus: a function required for the maintenance of the transformed state.Nature 227, 1021–1023.PubMedCrossRefGoogle Scholar
  52. Matsuse T., Namba Y., Ikeda K., Inoue S., Hosoi T., Ouchi Y., Fukuchi Y., and Orimo H. (1994) Immunohistochemical and in situ hybridisation detection of adenovirus early region 1A (ETA) gene in the microglia of human brain tissue.J. Clin. Pathol. 47, 275–277.PubMedCrossRefGoogle Scholar
  53. McCutchan J. H. and Pagano J. S. (1968) Enchancement of the infectivity of simian virus 40 deoxyribonucleic acid with diethyl-aminoethyl-dextran.J. Natl. Cancer Inst. 41, 351–357.PubMedGoogle Scholar
  54. Moreau-Gachelin F., Tavitian A., and Tambourin P. (1988) Spi-1 is a putative oncogene in virally induced murine erythroleukaemias.Nature 331, 277–280.PubMedCrossRefGoogle Scholar
  55. Morgenstern J. P. and Land H. (1990) Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.Nucleic Acids Res. 18, 3587–3596.PubMedCrossRefGoogle Scholar
  56. Mulligan R. C. and Berg P. (1980) Expression of a bacterial gene in mammalian cells.Science 209, 1422–1427.PubMedCrossRefGoogle Scholar
  57. Mulligan R. C. and Berg P. (1981) Selection for animal cells that express the E. coli gene coding for xanthine-guanine-phosphoribosyltransferase.Proc. Natl. Acad. Sci. USA 78, 2072–2076.PubMedCrossRefGoogle Scholar
  58. Mulligan R. C., Howard B. H., and Berg P. (1979) Synthesis of rabit β-globin in cultured monkey kidney cells following infection with a SV40 β-globin recombinant genome.Nature 277, 108–114.PubMedCrossRefGoogle Scholar
  59. Nandi A. K., Roginski R. S., Greeg R. G., Smithies O., and Skoultchi A. I. (1988) Regulated expression of genes inserted at the human chromosomal I3-globin locus by homologus recombination.Proc. Natl. Acad. Sci. USA 85, 3845–3849.PubMedCrossRefGoogle Scholar
  60. Neel B. G., Hayward W. S., Robinson H. L., Fang J., and Astrin S. M. (1981) Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion.Cell 23, 323–334.PubMedCrossRefGoogle Scholar
  61. Nussbaum A. L., Davoli D., Ganem D., and Fareed G. C. (1976) Construction and propagation of a defective simian virus 40 genome bearing an operator from bacteriophage lambda.Proc. Natl. Acad. Sci. USA 73, 1068–1072.PubMedCrossRefGoogle Scholar
  62. Onifer S. M., Whittemore S. R., and Holets V. R. (1993) Variable morphological differentiation of a rapine-derived neuronal cell line following transplantation into the adult rat CNS.Exp. Neurol. 122, 130–142.PubMedCrossRefGoogle Scholar
  63. Palella T. D., Hidaka Y., Silverman L. J., Levine M., Glorioso J., and Kelley W. N. (1989) Expression of human HPRT mRNA in brains of mice infected with a recombinant herpes simplex virus.Gene 80, 137–144.PubMedCrossRefGoogle Scholar
  64. Payne S. G., Courtneidge S. A., Crittenden L. B., Fadly A. M., Bishop J. M., and Varmus H. E. (1981) Analysis of avian leukosis virus DNA and RNA in bursar tumors: viral gene expression is not required for maintenance of tumor state.Cell 23, 311–322.PubMedCrossRefGoogle Scholar
  65. Perlow M. J., Freed W. J., Hoffer B. J., Seiger A., Olson L., and Wyatt R. J. (1979) Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system.Science 204, 643–646.PubMedCrossRefGoogle Scholar
  66. Renfranz P. J., Cunningham M. G., and McKay R. D. G. (1991) Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain.Cell 66, 713–729.PubMedCrossRefGoogle Scholar
  67. Revah F., Horellou P., Vigne E., Le Gal La Salle G., Robert J.-J., Perricaudet M., and Mallet J. (1996) Gene therapy of degenerative and genetic disorders of the central and peripheral nervous system using adenoviral vectors, inGene Transfer into Neurones—Towards Gene Therapy of Neurological Disorders (Lowenstein P. and Enquist L., eds.), Wiley, Chister, UK, pp. 81–92.Google Scholar
  68. Ridoux V., Robert J. J., Zhang X., Perricaudet M., Mallet J., and Le Gal La Salle G. (1994) Adenoviral vectors as functional retrograde neuronal tracers.Brain Res. 648, 171–175.PubMedCrossRefGoogle Scholar
  69. Rubin B. A. and Rorke L. B. (1988) Adenovirus vaccines, inVaccines (Plotkin J. E. and Mortimer L. A., eds.), Saunders, Philadelphia, PA, pp. 492–512.Google Scholar
  70. Sabate O., Horellou P., Vigne E., Colin P., Perricaudet M., Buc-Caron M. H., and Mallet J. (1995) Transplantation to the rat brain of human neural progenitors which were genetically modified using adenoviruses.Nature Genet. 9, 256–260.PubMedCrossRefGoogle Scholar
  71. Sauer H. and Oertel W. H. (1994) Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat.Neuroscience 59, 401–415.PubMedCrossRefGoogle Scholar
  72. Sauer H., Rosenblad C., and Bjorklund A. (1995) Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion.Proc. Natl. Acad. Sci. USA 92, 8935–8939.PubMedCrossRefGoogle Scholar
  73. Shimotohono K. and Temin H. M. (1981) Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus.Cell 26, 67–77.CrossRefGoogle Scholar
  74. Shinnick T. M., Lerner R. A., and Sutcliffe J.-G. (1981) Nucleotide sequence of Moloney murine leukemia virus.Nature 293, 543–548.PubMedCrossRefGoogle Scholar
  75. Shults C. W., Kimber T., and Martin D. (1996) Intrastriatal injection of GDNF attenuates the effects of 6-hydroxydopamine.NeuroReport 7, 627–631.PubMedCrossRefGoogle Scholar
  76. Smithies O., Gregg R. G., Boggs S. S., Koralewski M. A., and Kucherlapati R. S. (1985) Insertion of DNA sequences into the human chromosomal β-globin locus by homologus recombination.Nature 317, 230–234.PubMedCrossRefGoogle Scholar
  77. Snyder E. Y., Deitcher D. L., Walsh C., Arnold-Aldea S., Hartwieg E. A., and Cepko C. L. (1992) Multipotent neural cell lines can engraft and participate in development of mouse cerebellum.Cell 68, 33–51.PubMedCrossRefGoogle Scholar
  78. Teich N., Wyke J., and Kaplan P. (1985) Pathogenesis of retrQvirus-induced disease, inRNA Tumor Virus (Weiss R., Teich N., Varmus H., and Coffin J., eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 187–248.Google Scholar
  79. Temin H. M. and Mizutani S. (1970) RNA-dependent DNA polymerase in virions of Rous sarcoma virus.Nature 226, 1211–1213.PubMedCrossRefGoogle Scholar
  80. Thomas K. R., Folger K. R., and Capecchi M. R. (1986) High frequency targeting of genes to specific sites in the mammalian genome.Cell 44, 419–428.PubMedCrossRefGoogle Scholar
  81. Tomac A., Widenfalk J., Lin L.-F., Kohno T., Ebendal T., Hoffer B. J., and Olson L. (1995) Retrograde axonal transport of glial cell line-derived neurotrophic factor in the adult nigrostriatal system suggests a trophic role in the adult.Proc. Natl. Acad. Sci. USA 92, 8274–8278.PubMedCrossRefGoogle Scholar
  82. Uchida K., Ishii A., Kaneda N., Toya S., Nagatsu T., and Kohsaka S. (1990) Tetrahydrobiopterin-dependent production of L-DOPA in NRK fibroblasts transfected with tyrosine hydroxylase cDNA: future use for intracerebral grafting.Neurosci. Lett. 109, 282–286.PubMedCrossRefGoogle Scholar
  83. Ungerstedt U. and Arbuthnott G. W. (1970) Quantitative recording of rotational behavior in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system.Brain Res. 24, 485–493.PubMedCrossRefGoogle Scholar
  84. Vogt P. K. (1971) Genetically stable reassortment of markers during mixed infection with avian tumor viruses.Virology 46, 947–952.PubMedCrossRefGoogle Scholar
  85. Watanabe S. and Temin H. M. (1982) Encapsidation sequences for spleen necrosis virus, an avian retrovirus, are between the 5′ long terminal repeat and the start of the gag gene.Proc. Natl. Acad. Sci. USA 79, 5986–5990.PubMedCrossRefGoogle Scholar
  86. Wickham T. J., Filardo E. J., Cheresh D. A., and Nemerow G. R. (1994) Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization.J. Cell Biol. 127, 257–264.PubMedCrossRefGoogle Scholar
  87. Wickham T. J., Mathias P., Cheresh D. A., and Nemerow G. R. (1993) Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment.Cell 73, 309–319.PubMedCrossRefGoogle Scholar
  88. Wigler M., Sweet R., Sim G., Wold B., Pellicer A., Lacy E., Maniatis T., Silverstein S., and Axel R. (1979) Transformation of mammalian cells with genes from prokaryotes and eukaryotes.Cell 16, 777–785.PubMedCrossRefGoogle Scholar
  89. Winkler C., Sauer H., Lee C. S., and Bjorklund A. (1996) Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's Disease.J. Neurosci. 16, 7206–7215.PubMedGoogle Scholar
  90. Wolfe J. D., Deshmane S. L., and Fraser N. W. (1992) Herpes virus vector gene transfer and expression of β-glucuronidase in the central nervous system of MPS VII mice.Nature Genet. 1, 379–384.PubMedCrossRefGoogle Scholar
  91. Wolff J. A., Fisher L. J., Xu L., Jinnah H. A., Langlais P. J., Iuvone P. M., O'Malley K. L., Rosenberg M. B., Shimohama S., Friedmann T., and Gage F. H. (1989) Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease.Proc. Natl. Acad. Sci. USA 86, 9011–9014.PubMedCrossRefGoogle Scholar
  92. Yoshimoto Y., Lin Q., Collier T. J., Frim D. M., Breakefield X. O., and Bohn M. C. (1995) Astrocytes retrovirally transduced with BDNF elicit behavioral improvement in a rat model of Parkinson's disease.Brain Res. 691, 25–36.PubMedCrossRefGoogle Scholar
  93. Yu S.-F., von Runden T., Kantoff P. W., Garber C., Seiberg M., Ruther U., Anderson F. W., Wagner E. F., and Gilboa E. (1986) Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells.Proc. Natl. Acad. Sci. USA 83, 3194–3198.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 1997

Authors and Affiliations

  • Philippe Horellou
    • 1
  • Jacques Mallet
    • 1
  1. 1.C 9923 CNRS, Laboratoire de Génétique Moleculaire de la Neurotransmission et des Processus DégénératifsHopital de la Pitié SalpêtriereParisFrance

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