Retroviral-Mediated Gene Transfer and Duchenne Muscular Dystrophy

  • Matthew G. Dunckley
  • George Dickson


Over 70 human diseases have been named as potential beneficiaries of somatic cell gene therapy, ranging from inherited disorders, such as cystic fibrosis and forms of severe combined immune deficiency, to cancer and AIDS (Scarpa and Caskey, 1989). Intervention by ‘designer genes’ incorporated into patients’ own cells could replace absent or defective molecules, synthesize metabolic enzymes or drugs, or manipulate the body’s immune responses (Ledley, 1990; Miller, 1990a). The realisation that recombinant DNA technology, now familiar in a diagnostic context, can be applied to the correction of diagnosed diseases is leading to a renewed optimism in the clinic for treating conditions that have so far persistently defeated more conventional therapeutic strategies.


Muscular Dystrophy Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy Dystrophin Gene Duchenne Muscular Dystrophy Gene 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acsadi G, Dickson G, Love DR, Jani A, Walsh FS, Gurusinghe A, Wolff JA, Davies KE (1991): Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature 352: 815–818PubMedCrossRefGoogle Scholar
  2. Andersen KB, Nexo BA (1983): Entry of murine retrovirus into mouse fibroblasts. Virology 125: 85–98PubMedCrossRefGoogle Scholar
  3. Anderson JE, Bressler BH, Ovalle WK (1988): Functional regeneration in the hindlimb skeletal muscle of the mdx mouse. J Muse Res Cell Motil 9: 499–515CrossRefGoogle Scholar
  4. Anderson WF (1992): Human gene therapy. Science 256: 808–813PubMedCrossRefGoogle Scholar
  5. Armentano D, Yu S-F, Kantoff PW, von Ruden T, Anderson WF, Gilboa E (1987): Effect of internal viral sequences on the utility of retroviral vectors. J Virol 61: 1647–1650PubMedGoogle Scholar
  6. Bar S, Barnea E, Levy Z, Neuman S, Yaffe D, Nudel U (1990): A novel product of the Duehenne muscular dystrophy gene which greatly differs from the known isoforms in its structure and tissue distribution. Biochem J 272: 557–560PubMedGoogle Scholar
  7. Barnea E, Zuk D, Simantov R, Nudel U, Yaffe D (1990): Specificity of expression of the muscle and brain dystrophin gene promoters in muscle and brain cells. Neuron 5: 881–888PubMedCrossRefGoogle Scholar
  8. Barr E, Leiden JM (1991): Systemic delivery of recombinant proteins by genetically modified myoblasts. Science 254: 1507–1509PubMedCrossRefGoogle Scholar
  9. Battini J-L, Heard JM, Danos O (1992): Receptor choice determinants in the envelope glycoproteins of amphotropic, xenotropic and polytropic murine leukemia viruses. J Virol 66: 1468–1475PubMedGoogle Scholar
  10. Bender MA, Palmer TD, Gelinas RE, Miller AD (1987): Evidence that the packaging signal of Moloney murine leukemia virus exiends into the gag region. J Virol 61: 1639–1646PubMedGoogle Scholar
  11. Benoit PW, Belt WD (1970): Destruction and regeneration of skeletal muscle after treatment with a local anaesthetic, bupivacaine (MarcainR). JAnat 107: 547–556Google Scholar
  12. Bischoff R (1978): Myoblast fusion. In: Membrane Fusion. Cell Surface Reviews, Vol. 5: 127–179.Google Scholar
  13. Poste G, Nicolson GL,. Blake DJ, Love DR, Tinsley J, Morris GE, Turley H, Gatter K, Dickson G, Edwards YH, Davies ICE (1992): Characterisation of a 4.8 kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. Hum Mol Genet 1:103–109Google Scholar
  14. Bulfield G, Siller WG, Wight PAL, Moore KJ (1984): X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sei USA 81: 1189–1192CrossRefGoogle Scholar
  15. Carnwath JW, Shotton DW (1987): Muscular dystrophy in the mdx mouse: histopathology of the soleus and extensor digitorum longus muscles. J Neurol Sci 80: 39–54PubMedCrossRefGoogle Scholar
  16. Cepko C (1989): Lineage analysis in the vertebrate nervous system by retrovirus- mediated gene transfer. In: Cell Culture. Methods in Neurosciences, Vol. 1: 367–392.Google Scholar
  17. Conn PM, ed. San Diego, CA: Academic Press Chatis PA, Holland CA, Hartley JW, Rowe WP, Hopkins N (1983): Role for the 3 end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci USA 80: 4408–4411Google Scholar
  18. Cooper BJ, Winand NJ, Stedman H, Valentine B A, Hoffman EP, Kunkel LM, Scott M-O, Fischbeck KH, Kornegay JN, Avery RJ, Williams JR, Schmickel RD, Sylvester JE (1988): The homologue of the Duchenne locus is defective in X- linked muscular dystrophy of dogs. Nature 334: 154–156PubMedCrossRefGoogle Scholar
  19. Cornetta K, Morgan RA, Anderson WF (1991a): Safety issues related to retroviral-mediated gene transfer in humans. Hum Gene Ther 2: 5–14PubMedCrossRefGoogle Scholar
  20. Cornetta K, Morgan RA, Gillio A, Sturm S, Baltrucki L, O’Reilly R, Anderson WF (1991b): No retroviremia or pathology in long-term follow-up of monkeys exposed to a murine amphotropic retrovirus. Hum Gene Ther 2: 215–219PubMedCrossRefGoogle Scholar
  21. Danos O, Mulligan RC (1988): Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci USA 85: 6460–6464PubMedCrossRefGoogle Scholar
  22. DenDunnen JT, Backer E, VanOmmen GJB, Pearson PL (1989): The DMD gene analysed by field inversion gel electrophoresis. Br Med Bull 45: 644–658Google Scholar
  23. DenDunnen JT, Grootscholten PM, Dauwerse JG, Walker AP, Monaco AP, Butler R, Anand R, Coffey AJ, Bentley DR, Steensma HY, VanOmmen GJB (1992): Reconstruction of the 2.4 Mb human DMD-gene by homologous YAC recombination. Hum Mol Genet 1: 19–28CrossRefGoogle Scholar
  24. Dhawan J, Pan LC, Pavlath GK, Travis MA, Lanctot AM, Blau HM (1991): Systemic delivery of human growth hormone by injection of genetically engineered myoblasts. Science 254: 1509–1512PubMedCrossRefGoogle Scholar
  25. Dickson G, Love DR, Davies KE, Wells KE, Piper TA, Walsh FS (1991): Human dystrophin gene transfer: production and expression of a functional recombinant DNA-based gene. Human Genetics 88: 53–58PubMedCrossRefGoogle Scholar
  26. Dickson G, Azad A, Morris GE, Simon H, Noursadeghi M, Walsh FS (1992): Colocalisation and molecular association of dystrophin with laminin at the surface of mouse and human myotubes. J Cell Sci 103: 1223–1233PubMedGoogle Scholar
  27. Duchenne GBA (1868): Recherches sur la paralysie musculaire pseudohypertrophique ou paralysie myo-sclerosique. Arch Gen Med 11:5–25; 179–209; 305–321; 421–443; 552–588Google Scholar
  28. Duncan CJ (1989): Dystrophin and the integrity of the sarcolemma in Duchenne muscular dystrophy. Experientia 45: 175–177PubMedCrossRefGoogle Scholar
  29. Dunckley MG, Love DR, Davies KE, Walsh FS, Morris GE, Dickson, G (1992): Retroviral-mediated transfer of a dystrophin minigene into mdx myoblasts in vitro. FEBS Lett 296: 128–134PubMedCrossRefGoogle Scholar
  30. Dunckley MG, Wells DJ, Walsh FS, Dickson G (1993): Direct retroviral-mediated transfer of a dystrophin minigene into mdx mouse muscle in vivo. Hum Mol Genet 2: 717–723PubMedCrossRefGoogle Scholar
  31. Eglitis MA, Anderson WF (1988): Retroviral vectors for introduction of genes into mammalian cells. Biotechniques 6: 608–614PubMedGoogle Scholar
  32. Emery AEH (1988): Duchenne Muscular Dystrophy. ( 2nd edn. ). Oxford: Oxford University PressGoogle Scholar
  33. England SB, Nicholson LVB, Johnson MA, Forrest SM, Love DR, Zubrzycka-Gaarn EE, Bulman DE, Harris JB, Davies KE (1990): Very mild muscular dystrophy associated with deletion of 46% of dystrophin. Nature 343: 180–182PubMedCrossRefGoogle Scholar
  34. Ervasti JM, Ohlendieck K, Kahl SD, Gaver MG, Campbell KP (1990): Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature 345: 315–319PubMedCrossRefGoogle Scholar
  35. Ervasti JM, Campbell KP (1991): Membrane-organisation of the dystrophin-glycoprotein complex. Cell 66: 1121–1131PubMedCrossRefGoogle Scholar
  36. Feener CA, Koenig M, Kunkel LM (1989): Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus. Nature 338: 509–511PubMedCrossRefGoogle Scholar
  37. Gilbert MA, Charreau B, Vicart P, Paulin D, Nandi PK (1992): Mechanism of entry of a xenotropic MMuLV-derived recombinant retrovirus into porcine cells using the expression of the reporter nlslacZ gene. Arch Virol 124: 57–67PubMedCrossRefGoogle Scholar
  38. Gnirke A, Huxley C (1991): Transfer of the human HPRT and GART genes from yeast to mammalian cells by microinjection of YAC DNA. Som Cell Mol Genet 17: 573–580CrossRefGoogle Scholar
  39. Goldfarb MP, Weinberg RA(1981): Generation of novel, biologically active Harvey sarcoma viruses via apparent illegitimate recombination. J Virol 38: 136–150Google Scholar
  40. Goodrich DW, Duesberg PH (1990): Evidence that retroviral transduction is mediated by DNA, not by RNA. Proc Natl Acad Sci USA 87: 3604–3608PubMedCrossRefGoogle Scholar
  41. Grounds MD, McGeachie JK (1987): A model of myogenesis in vivo, derived from detailed autoradiographic studies of regenerating skeletal muscle, challenges the oncept of quantal mitosis. Cell Tissue Res 250: 563–569PubMedGoogle Scholar
  42. Grounds MD, Garrett KL, Lai MC, Wright W, Beilharz MW (1992): Identification of skeletal muscle precursor cells in vivo by use of MyoDl and myogenin probes. Cell Tissue Res 267: 99–104PubMedCrossRefGoogle Scholar
  43. Hall-Craggs ECB (1974): Rapid degeneration and regeneration of a whole skeletal muscle following treatment with bupivacaine (Marcain). Exp Neurol 43: 349–358PubMedCrossRefGoogle Scholar
  44. Hoffman EP, Brown RH, Kunkel LM (1987): Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51: 919–928PubMedCrossRefGoogle Scholar
  45. Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L, et al. (1988): Characterisation of dystrophin in muscle-biopsy specimens from patients with Duchenne’s and Becker’s muscular dystrophy. N Engl J Med 318: 1363–1368PubMedCrossRefGoogle Scholar
  46. Hwang SLH, Gilboa E (1984): Expression of genes introduced into cells by retroviral infection is more efficient than that of genes introduced into cells by DNA transfection. J Virol 50: 417–424PubMedGoogle Scholar
  47. Ibraghimov-Beskrovnaya O, Ervasti JM, Leveille CJ, Slaughter CA, Sernett SW, Campbell KP (1992): Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature 355: 696–702PubMedCrossRefGoogle Scholar
  48. Kim JW, Closs EI, Albritton LM, Cunningham JM (1991): Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. Nature 352: 725–728PubMedCrossRefGoogle Scholar
  49. Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM (1987): Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organisation of the DMD gene in normal and affected individuals. Cell 50: 509–517PubMedCrossRefGoogle Scholar
  50. Koenig M, Monaco AP, Kunkel LM (1988): The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53: 219–228PubMedCrossRefGoogle Scholar
  51. Kozak SL, Kabat D (1990): Ping-pong amplification of a retroviral vector achieves high-level gene expression: human growth hormone production. J Virol 64: 3500–3508PubMedGoogle Scholar
  52. Kulkosky J, Jones KS, Katz RA, Mack JPG, Skalka AM (1992): Residues critical for retroviral integrative recombination in a region that is highly conserved among retroviral/retrotransposon integrases and bacterial insertion sequence transposases. Mol Cell Biol 12: 2331–2338PubMedGoogle Scholar
  53. Ledley, FD (1990): Clinical application of somatic gene therapy in inborn errors of metabolism. J Inker Metab Dis 13: 597–616CrossRefGoogle Scholar
  54. Lee CC, Pearlman JA, Chamberlain JS, Caskey CT (1991): Expression of recombinant dystrophin and its localisation to the cell membrane. Nature 349: 334–336PubMedCrossRefGoogle Scholar
  55. Love DR, Flint TJ, Genet SA, Middleton-Price HR, Davies KE (1991): Becker muscular dystrophy patient with large intragenic dystrophin deletion: implications for functional minigenes and gene therapy. J Med Genet 28: 860–864PubMedCrossRefGoogle Scholar
  56. Lynch CM, Miller AD (1991): Production of high-titer helper virus-free retroviral vectors by cocultivation of packaging cells with different host ranges. J Virol 65: 3887–3890PubMedGoogle Scholar
  57. Mann R, Mulligan RC, Baltimore D (1983): Construction of a retrovirus packaging mutant and its use to produce helper free defective retrovirus. Cell 33: 153–159PubMedCrossRefGoogle Scholar
  58. Markowitz D, Goff S, Bank A (1988): A safe packaging cell line for gene transfer: separating viral genes on two different plasmids. J Virol 62: 1120–1124PubMedGoogle Scholar
  59. Mathes LE, Yohn DS, Olsen RG (1977): Purification of infectious feline leukemia virus from large volumes of tissue culture fluids. J Clin Micro 5: 372–374Google Scholar
  60. McGeachie JK, Grounds MD (1987): Initiation and duration of muscle precursor replication after mild and severe injury to skeletal muscle of mice: an autoradiographic study. Cell Tissue Res 248: 125–130PubMedCrossRefGoogle Scholar
  61. Miller AD, Rosman GJ (1989): Improved retroviral vectors for gene transfer and expression. Biotechniques 7: 980–990PubMedGoogle Scholar
  62. Miller AD (1990a): Progress toward human gene therapy. Blood 76: 271–278PubMedGoogle Scholar
  63. Miller AD (1990b): Retrovirus packaging cells. Hum Gene Ther 1: 5–14PubMedCrossRefGoogle Scholar
  64. Miller DG, Adam MA, Miller AD (1990c): Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 10: 4239–4242PubMedGoogle Scholar
  65. Morgenstern JP, Land H (1991): Choice and Manipulation of Retroviral Vectors. In: Gene Transfer and Expression Protocols. Methods in Molecular Biology, Vol. 7: 181–205.Google Scholar
  66. Murray EJ, ed. Clifton, NJ: Humana Press Nonaka I (1991): Progressive muscular dystrophy with particular reference to muscle regeneration. Acta Paediatr Jpn 33: 222–227Google Scholar
  67. Ohlendieck K, Campbell KP (1991): Dystrophin constitutes 5% of membrane cytoskeleton in skeletal muscle. FEBS Lett 283: 230–234PubMedCrossRefGoogle Scholar
  68. Partridge TA, Morgan JE, Coulton GR, Hoffman EP, Kunkel LM (1989): Conversion of mdx myofibers from dystrophin-negative to -positive by injection of normal myoblasts. Nature 337: 176–179PubMedCrossRefGoogle Scholar
  69. Partridge TA (1991a): Myoblast transfer: a possible therapy for inherited myopathies? Muscle Nerve 14: 197–212PubMedCrossRefGoogle Scholar
  70. Partridge TA (1991b): Animal models of muscular dystrophy - what can they teach us? Neuropath Appl Neurobiol 17: 353–363CrossRefGoogle Scholar
  71. Petropoulos CJ, Payne W, Salter DW, Hughes SH (1992): Appropriate in vivo expression of a muscle-specific promoter by using avian retroviral vectors for gene transfer. J Virol 66: 3391–3397PubMedGoogle Scholar
  72. Roses AD (1988): Mutants in Duchenne muscular dystrophy. Implications for prevention. Arch Neurol 45: 84–85PubMedCrossRefGoogle Scholar
  73. Scarpa M, Caskey CT (1989): The use of retroviral vectors in human disorders. In: Experimental Hematology Today - 1988, 81–91. Baum SJ, Dicke KA, Lotzova E, Pluznik DH,. New York: Springer-VerlagGoogle Scholar
  74. Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ (1989): The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244: 1578–1580PubMedCrossRefGoogle Scholar
  75. Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA, Petrof B, Narusawa M, Leferovich JM, Sladky JT, Kelly AM (1991): The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature 352: 536–539PubMedCrossRefGoogle Scholar
  76. Strauss WM, Jaenisch R (1992): Molecular complementation of a collagen mutation in mammalian cells using yeast artificial chromosomes. EMBO J 11: 417–421PubMedGoogle Scholar
  77. Suzuki A, Yoshida M, Yamamoto H, Ozawa E (1992): Glycoprotein-binding site of dystrophin is confined to the cysteine-rich domain and the first half of the carboxy-terminal domain. FEBS Lett 308: 154–160PubMedCrossRefGoogle Scholar
  78. Valentine BA, Cooper BJ, Cummings JF, DeLahunta A (1990): Canine X-linked muscular dystrophy: morphologic lesions. J Neurol Sci 97: 1–23PubMedCrossRefGoogle Scholar
  79. Varmus HE (1982): Form and function of retroviral proviruses. Science 216: 812–820PubMedCrossRefGoogle Scholar
  80. Wells DJ, Wells KE, Walsh FS, Davies KE, Goldspink G, Love DR, Chan-Thomas P, Dunckley MG, Piper T, Dickson G (1992): Human dystrophin expression corrects the myopathic phenotype in transgenic mdx mice. Hum Mol Genet 1: 35–40PubMedCrossRefGoogle Scholar
  81. Weiss R, Teich N, Varmus H, Coffin J (1984): RNA Tumor Viruses Cold Spring Harbor: Cold Spring Harbor Laboratory Google Scholar
  82. Wessel HB (1990): Dystrophin: a clinical perspective. Ped Neurol 6: 3–12Google Scholar
  83. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL (1990): Direct gene transfer into mouse muscle in vivo. Science 247: 1465–1468PubMedCrossRefGoogle Scholar
  84. Yoshimoto T, Yoshimoto E, Meruelo D (1992): Enhanced gene expression of the murine ecotropic retroviral receptor and its human homolog in proliferating cells. J Virol 66: 4377–4381PubMedGoogle Scholar

Copyright information

© Birkhäuser Boston 1994

Authors and Affiliations

  • Matthew G. Dunckley
  • George Dickson

There are no affiliations available

Personalised recommendations