Skip to main content
SpringerLink
Log in

Adeno-Associated Virus Based Gene Therapy in Skeletal Muscle

  • Protocol
Gene Targeting Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 133))

Abstract

Gene therapy, with the promise of symptomatic relief and curative potential, is being considered for a treatment of a wide variety of genetic and acquired diseases, with over 100 protocols approved by the National Institutes of Health since 1989. Skeletal muscle is an especially attractive target for gene therapy, because of its accessibility and capability to uptake, maintain, and express recombinant protein from plasmid DNA (1–7). Transduction of muscle has been considered for systemic delivery of recombinant proteins for treatment of anemia, inherited coagulopathies, endocrinologic disorders, and metabolic storage diseases, as well as localized delivery to treat dystrophinopathies and cardiovascular disorders (6–15). Numerous studies have already demonstrated expression in muscle of such transgenes as various reporter enzymes and relevant therapeutic proteins (1,3–5,16–18).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., and Felgner, P. L. (1990) Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468.

    Article  PubMed  CAS  Google Scholar 

  2. Wolff, J. A., Ludtke, J. J., Acsadi, G., Williams, P., and Jani, A. (1992) Longterm persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1, 363–369.

    Article  PubMed  CAS  Google Scholar 

  3. Jiao, S., Williams, P., Berg, R. K., Hodgeman, B. A., Liu, L., Repetto, G., and Wolff, J. A. (1992) Direct gene transfer into nonhuman primate myofibers in vivo. Hum. Gene Ther. 3, 21–33.

    Article  PubMed  CAS  Google Scholar 

  4. Ma, J. X., Yang, Z., Chao, J., and Chao, L. (1995) Intramuscular delivery of rat kallikrein-binding protein gene reverses hypotension in transgenic mice expressing human tissue kallikrein. J. Biol. Chem. 270, 451–455.

    Article  PubMed  Google Scholar 

  5. Mumper, R. J., Duguid, J. G., Anwer, K., Barron, M. K., Nitta, H., and Rolland, A. P. (1996) Polyvinyl derivatives as novel interactive polymers for controlled gene delivery to muscle. Pharm. Res. 13, 701–709.

    Article  PubMed  CAS  Google Scholar 

  6. Bartlett, R. J., Secore, S. L., Denis, M., Fernandez, L., Tzakis, A., Alejandro, R., and Ricordi, C. (1997) Toward the biologic release of human insulin from skeletal muscle. Transplant Proc. 29, 2199–2200.

    Article  PubMed  CAS  Google Scholar 

  7. Bartlett, R. J., Denis, M., Secore, S. L., Alejandro, R., and Ricordi, C. (1998) Toward engineering skeletal muscle to release peptide hormone from the human pre-proinsulin gene. Transplant Proc. 30, 451–452.

    Article  PubMed  CAS  Google Scholar 

  8. Dhawan, J., Pan, L. C., Pavlath, G. K., Travis, M. A., Lanctot, A. M., and Blau, H. M. (1991) Systemic delivery of human growth hormone by injection of genetically engineered myoblasts. Science 254, 1509–1512.

    Article  PubMed  CAS  Google Scholar 

  9. Dai, Y., Roman, M., Naviaux, R. K., and Verma, I. M. (1992) Gene therapy via primary myoblasts: long-term expression of factor IX protein following transplantation in vivo. Proc. Natl. Acad. Sci. USA 89, 10,892–10,895.

    Article  PubMed  CAS  Google Scholar 

  10. Yao, S. N. and Kurachi, K. (1992) Expression of human factor IX in mice after injection of genetically modified myoblasts. Proc. Natl. Acad. Sci. USA 89, 3357–3361.

    Article  PubMed  CAS  Google Scholar 

  11. Lozier, J. N. and Brinkhous, K. M. (1994) Gene therapy and the hemophilias. JAMA 271, 47–51.

    Article  PubMed  CAS  Google Scholar 

  12. Tripathy, S. K., Svensson, E. C., Black, H. B., Goldwasser, E., Margalith, M., Hobart, P. M., and Leiden, J. M. (1996) Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector. Proc. Natl. Acad. Sci. USA 93, 10,876–10,880.

    Article  PubMed  CAS  Google Scholar 

  13. Ledley, F. D. (1996) Pharmaceutical approach to somatic gene therapy. Pharm. Res. 13, 1595–1614.

    Article  PubMed  CAS  Google Scholar 

  14. Lee, C. C., Pons, F., Jones, P. G., Bies, R. D., Schlang, A. M., Leger, J. J., and Caskey, C. T. (1993) Mdx transgenic mouse: restoration of recombinant dystrophin to the dystrophic muscle. Hum. Gene Ther. 4, 273–281.

    Article  PubMed  CAS  Google Scholar 

  15. Davis, H. L., Whalen, R. G., and Demeneix, B. A. (1993) Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum. Gene Ther. 4, 151–159.

    Article  PubMed  Google Scholar 

  16. Davis, H. L., Michel, M. L., Mancini, M., Schleef, M., and Whalen, R. G. (1994) Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine 12, 1503–1509.

    Article  PubMed  CAS  Google Scholar 

  17. Manthorpe, M., Cornefert-Jensen, F., Hartikka, J., Felgner, J., Rundell, A., Margalith, M., and Dwarki, V. (1993) Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum. Gene Ther. 4, 419–431.

    Article  PubMed  CAS  Google Scholar 

  18. Bartlett, R. J., Secore, S. L., Singer, J. T., Bodo, M., Sharma, K., and Ricordi, C. (1996) Long-term expression of a fluorescent reporter gene via direct injection of plasmid vector into mouse skeletal muscle: comparison of human creatine kinase and CMV promoter expression levels in vivo. Cell Transplant 5, 411–419.

    Article  PubMed  CAS  Google Scholar 

  19. Dunckley, M. G., Wells, D. J., Walsh, F. S., and Dickson, G. (1993) Direct retroviral-mediated transfer of a dystrophin minigene into mdx mouse muscle in vivo. Hum. Mol. Genet. 2, 717–723.

    Article  PubMed  CAS  Google Scholar 

  20. Ragot, T., Vincent, N., Chafey, P., Vigne, E., Gilgenkrantz, H., Couton, D., et al. (1993) Efficient adenovirus-mediated transfer of a human mini-dystrophin gene to skeletal muscle of mdx mice. Nature 361, 647–650.

    Article  PubMed  CAS  Google Scholar 

  21. Vincent, N., Ragot, T., Gilgenkrantz, H., Couton, D., Chafey, P., Gregoire, A., et al. (1993) Long-term correction of mouse dystrophic degeneration by adenovirus-mediated transfer of a minidystrophin gene. Nature Genet. 5, 130–134.

    Article  PubMed  CAS  Google Scholar 

  22. Morishita, R., Gibbons, G. H., Kaneda, Y., Ogihara, T., and Dzau, V. J. (1993) Novel and effective gene transfer technique for study of vascular renin angiotensin system. J. Clin. Invest. 91, 2580–2585.

    Article  PubMed  CAS  Google Scholar 

  23. Kaneda, Y., Iwai, K., and Uchida, T. (1989) Introduction and expression of the human insulin gene in adult rat liver. J. Biol. Chem. 264, 12,126–12,129.

    PubMed  CAS  Google Scholar 

  24. Kaneda, Y., Iwai, K., and Uchida, T. (1989) Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science 243, 375–378.

    Article  PubMed  CAS  Google Scholar 

  25. Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., et al. (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA 84, 7413–7417.

    Article  PubMed  CAS  Google Scholar 

  26. Nabel, E. G., Gordon, D., Yang, Z. Y., Xu, L., San, H., Plautz, G. E., et al. (1992) Gene transfer in vivo with DNA-liposome complexes: lack of autoimmunity and gonadal localization. Hum. Gene Ther. 3, 649–656.

    Article  PubMed  CAS  Google Scholar 

  27. San, H., Yang, Z. Y., Pompili, V. J., Jaffe, M. L., Plautz, G. E., Xu, L., Felgner, J. H., Wheeler, C. J., et al. (1993) Safety and short-term toxicity of a novel cationic lipid formulation for human gene therapy. Hum. Gene Ther. 4, 781–788.

    Article  PubMed  CAS  Google Scholar 

  28. Levy, M. Y., Barron, L. G., Meyer, K. B., and Szoka, F. C., Jr. (1996) Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Ther. 3, 201–211.

    PubMed  CAS  Google Scholar 

  29. Nabel, E. G., Plautz, G., Boyce, F. M., Stanley, J. C., and Nabel, G. J. (1989) Recombinant gene expression in vivo within endothelial cells of the arterial wall. Science 244, 1342–1344.

    Article  PubMed  CAS  Google Scholar 

  30. Nelson, D. L., Ledbetter, S. A., Corbo, L., Victoria, M. F., Ramirez-Solis, R., Webster, T. D., Ledbetter, D. H., and Caskey, C. T. (1989) Alu polymerase chain reaction: a method for rapid isolation of human-specific sequences from complex DNA sources. Proc. Natl. Acad. Sci. USA 86, 6686–6690.

    Article  PubMed  CAS  Google Scholar 

  31. Hock, R. A. and Miller, A. D. (1986) Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells. Nature 320, 275–277.

    Article  PubMed  CAS  Google Scholar 

  32. Cone, R. D. and Mulligan, R. C. (1984) High-efficiency gene transfer into mammalian cells: generation of helper-free recombinant retrovirus with broad mammalian host range. Proc. Natl. Acad. Sci. USA 81, 6349–6353.

    Article  PubMed  CAS  Google Scholar 

  33. Naldini, L., Blomer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., and Trono, D. (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263–267.

    Article  PubMed  CAS  Google Scholar 

  34. Dai, Y., Schwarz, E. M., Gu, D., Zhang, W. W., Sarvetnick, N., and Verma, I. M. (1995) Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression. Proc. Natl. Acad. Sci. USA 92, 1401–1405.

    Article  PubMed  CAS  Google Scholar 

  35. Yang, Y., Nunes, F. A., Berencsi, K., Furth, E. E., Gonczol, E., and Wilson, J. M. (1994) Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc. Natl. Acad. Sci. USA 91, 4407–4411.

    Article  PubMed  CAS  Google Scholar 

  36. Muzyczka, N. (1992) Use of adeno-associated virus as a general transduction vector for mammalian cells. Curr. Top. Microbiol. Immunol. 158, 97–129.

    PubMed  CAS  Google Scholar 

  37. Flotte, T. R. and Carter, B. J. (1995) Adeno-associated virus vectors for gene therapy. Gene Ther. 2, 357–362.

    PubMed  CAS  Google Scholar 

  38. Xiao, X., Li, J., McCown, T. J., and Samulski, R. J. (1997) Gene transfer by adenoassociated virus vectors into the central nervous system. Exp. Neurol. 144, 113–124.

    Article  PubMed  CAS  Google Scholar 

  39. Kaplitt, M. G. and Makimura, H. (1997) Defective viral vectors as agents for gene transfer in the nervous system. J. Neurosci. Methods 71, 125–132.

    Article  PubMed  CAS  Google Scholar 

  40. Wagner, J. A. and Gardner, P. (1997) Toward cystic fibrosis gene therapy. Annu. Rev. Med. 48, 203–216.

    Article  PubMed  CAS  Google Scholar 

  41. Xiao, X., deVlamink, W., and Monahan, J. (1993) Adeno-associated virus (AAV) vectors for gene transfer. Adv. Drug Deliv. Rev. 12, 201–215.

    Article  CAS  Google Scholar 

  42. Flotte, T. R., Afione, S. A., and Zeitlin, P. L. (1994) Adeno-associated virus vector gene expression occurs in nondividing cells in the absence of vector DNA integration. Am. J. Respir. Cell Mol. Biol. 11, 517–521.

    PubMed  CAS  Google Scholar 

  43. Podsakoff, G., Wong, K. K., Jr., and Chatterjee, S. (1994) Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors. J. Virol. 68, 5656–5666.

    PubMed  CAS  Google Scholar 

  44. Russell, D. W., Miller, A. D., and Alexander, I. E. (1994) Adeno-associated virus vectors preferentially transduce cells in S phase. Proc. Natl. Acad. Sci. USA 91, 8915–8919.

    Article  PubMed  CAS  Google Scholar 

  45. Halbert, C. L., Alexander, I. E., Wolgamot, G. M., and Miller, A. D. (1995) Adeno-associated virus vectors transduce primary cells much less efficiently than immortalized cells. J. Virol. 69, 1473–1479.

    PubMed  CAS  Google Scholar 

  46. Blacklow, N. R., Hoggan, M. D., and Rowe, W. P. (1968) Serologic evidence for human infection with adenovirus-associated viruses. J. Natl. Cancer Inst. 40, 319–327.

    PubMed  CAS  Google Scholar 

  47. Berns, K. I. and Bohenzky, R. A. (1987) Adeno-associated viruses: an update. Adv. Virus Res. 32, 243–306.

    Article  PubMed  CAS  Google Scholar 

  48. Berns, K. I. and Linden, R. M. (1995) Cryptic life style of adeno-associated virus. Bioessays 17, 237–245.

    Article  PubMed  CAS  Google Scholar 

  49. Walz, C. and Schlehofer, J. R. (1992) Modification of some biological properties of HeLa cells containing adeno-associated virus DNA integrated into chromosome 19. J. Virol. 66, 2990–3002.

    PubMed  CAS  Google Scholar 

  50. Flotte, T. R., Solow, R., Owens, R. A., Afione, S., Zeitlin, P. L., and Carter, B. J. (1992) Gene expression from adeno-associated virus vectors in airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 7, 349–356.

    PubMed  CAS  Google Scholar 

  51. Tamayose, K., Hirai, Y., and Shimada, T. (1996) New strategy for large-scale preparation of high-titer recombinant adeno-associated virus vectors by using packaging cell lines and sulfonated cellulose column chromatography. Hum. Gene Ther. 7, 507–513.

    Article  PubMed  CAS  Google Scholar 

  52. Inoue, N. and Russell, D. W. (1998) Packaging cells based on inducible gene amplification for the production of adeno-associated virus vectors. J. Virol. 72, 7024–7031.

    PubMed  CAS  Google Scholar 

  53. Salvetti, A., Oreve, S., Chadeuf, G., Favre, D., Cherel, Y., Champion-Arnaud, P., David-Ameline, J., and Moullier, P. (1998) Factors influencing recombinant adeno-associated virus production. Hum. Gene Ther. 9, 695–706.

    Article  PubMed  CAS  Google Scholar 

  54. Ding, L., Lu, S., and Munshi, N. C. (1997) In vitro packaging of an infectious recombinant adeno-associated virus 2. Gene Ther. 4, 1167–1172.

    Article  PubMed  CAS  Google Scholar 

  55. Conway, J. E., Zolotukhin, S., Muzyczka, N., Hayward, G. S., and Byrne, B. J. (1997) Recombinant adeno-associated virus type 2 replication and packaging is entirely supported by a herpes simplex virus type 1 amplicon expressing Rep and Cap. J. Virol. 71, 8780–8789.

    PubMed  CAS  Google Scholar 

  56. Xiao, X., Li, J., and Samulski, R. J. (1998) Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J. Virol. 72, 2224–2232.

    PubMed  CAS  Google Scholar 

  57. Kessler, P. D., Podsakoff, G. M., Chen, X., McQuiston, S. A., Colosi, P. C., Matelis, L. A., Kurtzman, G. J., and Byrne, B. J. (1996) Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc. Natl. Acad. Sci. USA 93, 14,082–14,087.

    Article  PubMed  CAS  Google Scholar 

  58. McLaughlin, S. K., Collis, P., Hermonat, P. L., and Muzyczka, N. (1988) Adenoassociated virus general transduction vectors: analysis of proviral structures. J. Virol. 62, 1963–1973.

    PubMed  CAS  Google Scholar 

  59. Samulski, R. J., Chang, L. S., and Shenk, T. (1989) Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. J. Virol. 63, 3822–3828.

    PubMed  CAS  Google Scholar 

  60. Siegl, G., Bates, R. C., Berns, K. I., Carter, B. J., Kelly, D. C., Kurstak, E., and Tattersall, P. (1985) Characteristics and taxonomy of Parvoviridae. Intervirology 23, 61–73.

    Article  PubMed  CAS  Google Scholar 

  61. Berns, K. I. (1990) Parvovirus replication. Microbiol. Rev. 54, 316–329.

    PubMed  CAS  Google Scholar 

  62. Atchinson, R. W., Casto, B. C., and Hammond, W. M. (1965) Adeno-associated defective virus particles. Science 149, 754–756.

    Article  Google Scholar 

  63. Hoggan, M. D., Blacklow, N. R., and Rowe, W. P. (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc. Natl. Acad. Sci. USA 55, 1467–1474.

    Article  PubMed  CAS  Google Scholar 

  64. Handa, H., Shiroki, K., and Shimojo, H. (1977) Establishment and characterization of KB cell lines latently infected with adeno-associated virus type 1. Virology 82, 84–92.

    Article  PubMed  CAS  Google Scholar 

  65. Cheung, A. K., Hoggan, M. D., Hauswirth, W. W., and Berns, K. I. (1980) Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. J. Virol. 33, 739–748.

    PubMed  CAS  Google Scholar 

  66. Yakinoglu, A. O., Heilbronn, R., Burkle, A., Schlehofer, J. R., and zur Hausen, H. (1988) DNA amplification of adeno-associated virus as a response to cellular genotoxic stress. Cancer Res. 48, 3123–3129.

    Google Scholar 

  67. Yakobson, B., Koch, T., and Winocour, E. (1987) Replication of adenoassociated virus in synchronized cells without the addition of a helper virus. J. Virol. 61, 972–981.

    PubMed  CAS  Google Scholar 

  68. Yakobson, B., Hrynko, T. A., Peak, M. J., and Winocour, E. (1989) Replication of adeno-associated virus in cells irradiated with UV light at 254 nm. J. Virol. 63, 1023–1030.

    PubMed  CAS  Google Scholar 

  69. Walz, C., Schlehofer, J. R., Flentje, M., Rudat, V., and zur Hausen, H. (1992) Adeno-associated virus sensitizes HeLa cell tumors to gamma rays. J. Virol. 66, 5651–5657.

    Google Scholar 

  70. Rutledge, E. A., Halbert, C. L., and Russell, D. W. (1998) Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. J. Virol. 72, 309–319.

    PubMed  CAS  Google Scholar 

  71. Summerford, C. and Samulski, R. J. (1998) Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J. Virol. 72, 1438–1445.

    PubMed  CAS  Google Scholar 

  72. Srivastava, A., Lusby, E. W., and Berns, K. I. (1983) Nucleotide sequence and organization of the adeno-associated virus 2 genome. J. Virol. 45, 555–564.

    PubMed  CAS  Google Scholar 

  73. Cassinotti, P., Weitz, M., and Tratschin, J. D. (1988) Organization of the adenoassociated virus (AAV) capsid gene: mapping of a minor spliced mRNA coding for virus capsid protein 1. Virology 167, 176–184.

    Article  CAS  Google Scholar 

  74. Becerra, S. P., Koczot, F., Fabisch, P., and Rose, J. A. (1988) Synthesis of adenoassociated virus structural proteins requires both alternative mRNA splicing and alternative initiations from a single transcript. J. Virol. 62, 2745–2754.

    PubMed  CAS  Google Scholar 

  75. Muralidhar, S., Becerra, S. P., and Rose, J. A. (1994) Site-directed mutagenesis of adeno-associated virus type 2 structural protein initiation codons: effects on regulation of synthesis and biological activity. J. Virol. 68, 170–176.

    PubMed  CAS  Google Scholar 

  76. Mendelson, E., Trempe, J. P., and Carter, B. J. (1986) Identification of the transacting Rep proteins of adeno-associated virus by antibodies to a synthetic oligopeptide. J. Virol. 60, 823–832.

    PubMed  CAS  Google Scholar 

  77. Tratschin, J. D., Miller, I. L., and Carter, B. J. (1984) Genetic analysis of adeno-associated virus: properties of deletion mutants constructed in vitro and evidence for an adeno-associated virus replication function. J. Virol. 51, 611–619.

    PubMed  CAS  Google Scholar 

  78. Owens, R. A. and Carter, B. J. (1992) In vitro resolution of adeno-associated virus DNA hairpin termini by wild-type Rep protein is inhibited by a dominantnegative mutant of rep. J. Virol. 66, 1236–1240.

    PubMed  CAS  Google Scholar 

  79. Hermonat, P. L., Labow, M. A., Wright, R., Berns, K. I., and Muzyczka, N. (1984) Genetics of adeno-associated virus: isolation and preliminary characterization of adeno-associated virus type 2 mutants. J. Virol. 51, 329–339.

    PubMed  CAS  Google Scholar 

  80. Senapathy, P., Tratschin, J. D., and Carter, B. J. (1984) Replication of adenoassociated virus DNA. Complementation of naturally occurring rep-mutants by a wild-type genome or an ori-mutant and correction of terminal palindrome deletions. J. Mol. Biol. 179, 1–20.

    Article  PubMed  CAS  Google Scholar 

  81. Gottlieb, J. and Muzyczka, N. (1988) In vitro excision of adeno-associated virus DNA from recombinant plasmids: isolation of an enzyme fraction from HeLa cells that cleaves DNA at poly(G) sequences. Mol. Cell Biol. 8, 2513–2522.

    PubMed  CAS  Google Scholar 

  82. Hong, G., Ward, P., and Berns, K. I. (1992) In vitro replication of adenoassociated virus DNA. Proc. Natl. Acad. Sci. USA 89, 4673–4677.

    Article  PubMed  CAS  Google Scholar 

  83. Hong, G., Ward, P., and Berns, K. I. (1994) Intermediates of adeno-associated virus DNA replication in vitro. J. Virol. 68, 2011–2015.

    PubMed  CAS  Google Scholar 

  84. Samulski R. J., Berns K. I., Tan M., and Muzyczka N. (1982) Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells. Proc. Natl. Acad. Sci. USA 79, 2077–2081.

    Article  PubMed  CAS  Google Scholar 

  85. Samulski R. J., Srivastava A., Berns K. I., and Muzyczka N. (1983) Rescue of adeno-associated virus from recombinant plasmids: gene correction within the terminal repeats of AAV. Cell 33, 135–143.

    Article  PubMed  CAS  Google Scholar 

  86. Lusby E., Fife K. H., and Berns K. I. (1980) Nucleotide sequence of the inverted terminal repetition in adeno-associated virus DNA. J. Virol. 34, 402–409.

    PubMed  CAS  Google Scholar 

  87. Ni T. H., Zhou X., McCarty D. M., Zolotukhin I., and Muzyczka N. (1994) In vitro replication of adeno-associated virus DNA. J. Virol. 68, 1128–1138.

    PubMed  CAS  Google Scholar 

  88. Srivastava A (1987) Replication of the adeno-associated virus DNA termini in vitro. Intervirology 27, 138–147.

    Article  PubMed  CAS  Google Scholar 

  89. Wang X. S. and Srivastava A. (1998) Rescue and autonomous replication of adeno-associated virus type 2 genomes containing Rep binding site mutations in the viral p5 promoter. J. Virol. 72, 4811–4818.

    PubMed  CAS  Google Scholar 

  90. Qing K., Khuntirat B., Mah C., Kube D. M., Wang X. S., Ponnazhagan S., et al. (1998) Adeno-associated virus type 2-mediated gene transfer: correlation of tyrosine phosphorylation of the cellular single-stranded D sequence-binding protein with transgene expression in human cells in vitro and murine tissues in vivo. J. Virol. 72, 1593–1599.

    PubMed  CAS  Google Scholar 

  91. Qing K., Wang X. S., Kube D. M., Ponnazhagan S., Bajpai A., and Srivastava A. (1997) Role of tyrosine phosphorylation of a cellular protein in adeno-associated virus 2-mediated transgene expression. Proc. Natl. Acad. Sci. USA 94, 10,879–10,884.

    Article  PubMed  CAS  Google Scholar 

  92. Im D. S. and Muzyczka N. (1990) AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell 61, 447–457.

    Article  PubMed  CAS  Google Scholar 

  93. Leonard C. J. and Berns K. I. (1994) Adeno-associated virus type 2: a latent life cycle. Prog. Nucleic Acid Res. Mol. Biol. 48, 29–52.

    Article  PubMed  CAS  Google Scholar 

  94. Labow M. A. and Berns K. I. (1988) Adeno-associated virus rep gene inhibits replication of an adeno-associated virus/simian virus 40 hybrid genome in cos-7 cells. J. Virol. 62, 1705–1712.

    PubMed  CAS  Google Scholar 

  95. Berns K. I., Kotin R. M., and Labow M. A. (1988) Regulation of adenoassociated virus DNA replication. Biochim. Biophys. Acta. 951, 425–429.

    PubMed  CAS  Google Scholar 

  96. Beaton A., Palumbo P., and Berns K. I. (1989) Expression from the adenoassociated virus p5 and p19 promoters is negatively regulated in trans by the rep protein. J. Virol. 63, 4450–4454.

    PubMed  CAS  Google Scholar 

  97. Linden R. M., Ward P., Giraud C., Winocour E., and Berns K. I. (1996) Sitespecific integration by adeno-associated virus. Proc. Natl. Acad. Sci. USA 93, 11,288–11,294.

    Article  PubMed  CAS  Google Scholar 

  98. Kotin R. M. and Berns K. I. (1989) Organization of adeno-associated virus DNA in latently infected Detroit 6 cells. Virology 170, 460–467.

    Article  PubMed  CAS  Google Scholar 

  99. Kotin R. M., Menninger J. C., Ward D. C., and Berns K. I. (1991) Mapping and direct visualization of a region-specific viral DNA integration site on chromosome 19q13-qter. Genomics 10, 831–834.

    Article  PubMed  CAS  Google Scholar 

  100. Kotin R. M., Siniscalco M., Samulski R. J., Zhu X. D., Hunter L., Laughlin C. A., et al. (1990) Site-specific integration by adeno-associated virus. Proc. Natl. Acad. Sci. USA 87, 2211–2215.

    Article  PubMed  CAS  Google Scholar 

  101. Laughlin C. A., Cardellichio C. B., and Coon H. C. (1986) Latent infection of KB cells with adeno-associated virus type 2. J. Virol. 60, 515–524.

    PubMed  CAS  Google Scholar 

  102. Samulski R. J., Zhu X., Xiao X., Brook J. D., Housman D. E., Epstein N., and Hunter L. A. (1991) Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J. 10, 3941–3950.

    PubMed  CAS  Google Scholar 

  103. Buller R. M., Janik J. E., Sebring E. D., and Rose J. A. (1981) Herpes simplex virus types 1 and 2 completely help adenovirus-associated virus replication. J. Virol. 40, 241–247.

    PubMed  CAS  Google Scholar 

  104. Schlehofer J. R., Ehrbar M., and zur Hausen H. (1986) Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus. Virology 152, 110–117.

    Article  PubMed  CAS  Google Scholar 

  105. Chiorini J. A., Wiener S. M., Yang L., Smith R. H., Safer B., Kilcoin N. P., et al. (1996) Roles of AAV Rep proteins in gene expression and targeted integration. Curr. Top. Microbiol. Immunol. 218, 25–33.

    PubMed  CAS  Google Scholar 

  106. Wang X. S. and Srivastava A. (1997) A novel terminal resolution-like site in the adeno-associated virus type 2 genome. J. Virol. 71, 1140–1146.

    PubMed  CAS  Google Scholar 

  107. Ni T. H., McDonald W. F., Zolotukhin I., Melendy T., Waga S., Stillman B., and Muzyczka N. (1998) Cellular proteins required for adeno-associated virus DNA replication in the absence of adenovirus coinfection. J. Virol. 72, 2777–2787.

    PubMed  CAS  Google Scholar 

  108. Kotin R. M., Linden R. M., and Berns K. I. (1992) Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO J. 11, 5071–5078.

    PubMed  CAS  Google Scholar 

  109. Giraud C., Winocour E., and Berns K. I. (1994) Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence. Proc. Natl. Acad. Sci. USA 91, 10,039–10,043.

    Article  PubMed  CAS  Google Scholar 

  110. Weitzman M. D., Kyostio S. R., Kotin R. M., and Owens R. A. (1994) Adenoassociated virus (AAV) Rep proteins mediate complex formation between AAV DNA and its integration site in human DNA. Proc. Natl. Acad. Sci. USA 91, 5808–5812.

    Article  PubMed  CAS  Google Scholar 

  111. Chiorini J. A., Wiener S. M., Owens R. A., Kyostio S. R., Kotin R. M., and Safer B. (1994) Sequence requirements for stable binding and function of Rep68 on the adeno-associated virus type 2 inverted terminal repeats. J. Virol. 68, 7448–7457.

    PubMed  CAS  Google Scholar 

  112. Snyder R. O., Im D. S., Ni T., Xiao X., Samulski R. J., and Muzyczka N. (1993) Features of the adeno-associated virus origin involved in substrate recognition by the viral Rep protein. J. Virol. 67, 6096–6104.

    PubMed  CAS  Google Scholar 

  113. Berns K. I. (1996) in Papoviridae: The Viruses and Their Replication, vol. 2 (Fields B. N., Knipe D. M., and Howley P. M., eds.), Lippincott-Raven Philadelphia, pp. 2173–2220.

    Google Scholar 

  114. Wonderling R. S. and Owens R. A. (1997) Binding sites for adeno-associated virus Rep proteins within the human genome. J. Virol. 71, 2528–2534.

    PubMed  CAS  Google Scholar 

  115. Surosky, R. T., Urabe, M., Godwin, S. G., McQuiston, S. A., Kurtzman, G. J., Ozawa, K., and Natsoulis, G. (1997) Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome. J. Virol. 71, 7951–7959.

    PubMed  CAS  Google Scholar 

  116. Xiao, X., Li, J., and Samulski, R. J. (1996) Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J. Virol. 70, 8098–8108.

    PubMed  CAS  Google Scholar 

  117. Clark, K. R., Sferra, T. J., and Johnson, P. R. (1997) Recombinant adeno-associated viral vectors mediate long-term transgene expression in muscle. Hum. Gene Ther. 8, 659–669.

    Article  PubMed  CAS  Google Scholar 

  118. Fisher, K. J., Jooss, K., Alston, J., Yang, Y., Haecker, S. E., High, K., Pathak, R., Raper, S. E., and Wilson, J. M. (1997) Recombinant adeno-associated virus for muscle directed gene therapy. Nature Med. 3, 306–312.

    Article  PubMed  CAS  Google Scholar 

  119. Herzog, R. W., Hagstrom, J. N., Kung, S. H., Tai, S. J., Wilson, J. M., Fisher, K. J., and High, K. A. (1997) Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adenoassociated virus. Proc. Natl. Acad. Sci. USA 94, 5804–5809.

    Article  PubMed  CAS  Google Scholar 

  120. Monahan, P. E., Samulski, R. J., Tazelaar, J., Xiao, X., Nichols, T. C., Bellinger, D. A., Read, M. S., and Walsh, C. E. (1998) Direct intramuscular injection with recombinant AAV vectors results in sustained expression in a dog model of hemophilia. Gene Ther. 5, 40–49.

    Article  PubMed  CAS  Google Scholar 

  121. 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.

    Article  PubMed  CAS  Google Scholar 

  122. McCown, T. J., Xiao, X., Li, J., Breese, G. R., and Samulski, R. J. (1996) Differential and persistent expression patterns of CNS gene transfer by an adenoassociated virus (AAV) vector. Brain Res. 713, 99–107.

    Article  PubMed  CAS  Google Scholar 

  123. Kaplitt, M. G. and Pfaff, D. W. (1996) Viral vectors for gene delivery and expression in the CNS. Methods 10, 343–350.

    Article  PubMed  CAS  Google Scholar 

  124. Flannery, J. G., Zolotukhin, S., Vaquero, M. I., LaVail, M. M., Muzyczka, N., and Hauswirth, W. W. (1997) Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc. Natl. Acad. Sci. USA 94, 6916–6921.

    Article  PubMed  CAS  Google Scholar 

  125. Flotte, T. R., Afione, S. A., Solow, R., Drumm, M. L., Markakis, D., Guggino, W. B., Zeitlin, P. L., and Carter, B. J. (1993) Expression of the cystic fibrosis transmembrane conductance regulator from a novel adeno-associated virus promoter. J. Biol. Chem. 268, 3781–3790.

    PubMed  CAS  Google Scholar 

  126. Afione, S. A., Conrad, C. K., Kearns, W. G., Chunduru, S., Adams, R., Reynolds, T. C., et al. (1996) In vivo model of adeno-associated virus vector persistence and rescue. J. Virol. 70, 3235–3241.

    PubMed  CAS  Google Scholar 

  127. Koeberl, D. D., Alexander, I. E., Halbert, C. L., Russell, D. W., and Miller, A. D. (1997) Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors. Proc. Natl. Acad. Sci. USA 94, 1426–1431.

    Article  PubMed  CAS  Google Scholar 

  128. Snyder, R. O., Miao, C. H., Patijn, G. A., Spratt, S. K., Danos, O., Nagy, D., Gown, A. M., Winther, B., Meuse, L., Cohen, L. K., Thompson, A. R., and Kay, M. A. (1997) Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors. Nature Genet. 16, 270–276.

    Article  PubMed  CAS  Google Scholar 

  129. Shaughnessy, E., Lu, D., Chatterjee, S., and Wong, K. K. (1996) Parvoviral vectors for the gene therapy of cancer. Semin. Oncol. 23, 159–171.

    PubMed  CAS  Google Scholar 

  130. Wong, K. K., Jr. and Chatterjee, S. (1996) Adeno-associated virus based vectors as antivirals. Curr. Top. Microbiol. Immunol. 218, 145–170.

    PubMed  CAS  Google Scholar 

  131. Russell, D. W. and Hirata, R. K. (1998) Human gene targeting by viral vectors. Nature Genet. 18, 325–330.

    Article  PubMed  CAS  Google Scholar 

  132. Xiao, X., Xiao, W., Li, J., and Samulski, R. J. (1997) Novel 165-base-pair terminal repeat sequence is the sole cis requirement for the adeno-associated virus life cycle. J. Virol. 71, 941–948.

    PubMed  CAS  Google Scholar 

  133. Bowers, W. J., Howard, D. F., and Federoff, H. J. (1997) Gene therapeutic strategies for neuroprotection: implications for Parkinson’s disease. Exp. Neurol. 144, 58–68.

    Article  PubMed  CAS  Google Scholar 

  134. Kohn, D. B. (1997) Gene therapy for haematopoietic and lymphoid disorders. Clin Exp Immunol. 107(Suppl 1), 54–57.

    PubMed  Google Scholar 

  135. Duan, D., Fisher, K. J., Burda, J. F., and Engelhardt, J. F. (1997) Structural and functional heterogeneity of integrated recombinant AAV genomes. Virus Res. 48, 41–56.

    Article  PubMed  CAS  Google Scholar 

  136. Samulski, R. J. (1993) Adeno-associated virus: integration at a specific chromosomal locus. Curr. Opin. Genet. Dev. 3, 74–80.

    Article  PubMed  CAS  Google Scholar 

  137. Walsh, C. E., Liu, J. M., Xiao, X., Young, N. S., Nienhuis, A. W., and Samulski, R. J. (1992) Regulated high level expression of a human gamma-globin gene introduced into erythroid cells by an adeno-associated virus vector. Proc. Natl. Acad. Sci. USA. 89, 7257–7261.

    Article  PubMed  CAS  Google Scholar 

  138. Rutledge, E. A. and Russell, D. W. (1997) Adeno-associated virus vector integration junctions. J. Virol. 71, 8429–8436.

    PubMed  CAS  Google Scholar 

  139. Wu, P., Phillips, M. I., Bui, J., and Terwilliger, E. F. (1998) Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets. J. Virol. 72, 5919–5926.

    PubMed  CAS  Google Scholar 

  140. Minami, M., Poussin, K., Brechot, C., and Paterlini, P. (1995) Novel PCR technique using Alu-specific primers to identify unknown flanking sequences from the human genome. Genomics 29, 403–408.

    Article  PubMed  CAS  Google Scholar 

  141. Kube, D. M., Ponnazhagan, S., and Srivastava, A. (1997) Encapsidation of adeno-associated virus type 2 Rep proteins in wild-type and recombinant progeny virions: Rep-mediated growth inhibition of primary human cells. J. Virol. 71, 7361–7371.

    PubMed  CAS  Google Scholar 

  142. Prasad, K. M. and Trempe, J. P. (1995) Adeno-associated virus Rep78 protein is covalently linked to viral DNA in a preformed virion. Virology 214, 360–370.

    Article  PubMed  CAS  Google Scholar 

  143. Ferrari, F. K., Samulski, T., Shenk, T., and Samulski, R. J. (1996) Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adenoassociated virus vectors. J. Virol. 70, 3227–3234.

    PubMed  CAS  Google Scholar 

  144. Fisher, K. J., Gao, G. P., Weitzman, M. D., DeMatteo, R., Burda, J. F., and Wilson, J. M. (1996) Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis. J. Virol. 70, 520–532.

    PubMed  CAS  Google Scholar 

  145. Alexander, I. E., Russell, D. W., and Miller, A. D. (1994) DNA-damaging agents greatly increase the transduction of nondividing cells by adeno-associated virus vectors. J. Virol. 68, 8282–8287.

    PubMed  CAS  Google Scholar 

  146. Alexander, I. E., Russell, D. W., Spence, A. M., and Miller, A. D. (1996) Effects of gamma irradiation on the transduction of dividing and nondividing cells in brain and muscle of rats by adeno-associated virus vectors. Hum. Gene Ther. 7, 841–850.

    Article  PubMed  CAS  Google Scholar 

  147. Fisher, K. J., Kelley, W. M., Burda, J. F., and Wilson, J. M. (1996) Novel adenovirus-adeno-associated virus hybrid vector that displays efficient rescue and delivery of the AAV genome. Hum. Gene Ther. 7, 2079–2087.

    Article  PubMed  CAS  Google Scholar 

  148. Wilson, J. M., Birinyi, L. K., Salomon, R. N., Libby, P., Callow, A. D., and Mulligan, R. C. (1989) Implantation of vascular grafts lined with genetically modified endothelial cells. Science 244, 1344–1346.

    Article  PubMed  CAS  Google Scholar 

  149. Crystal, R. G. (1995) Transfer of genes to humans: early lessons and obstacles to success. Science 270, 404–410.

    Article  PubMed  CAS  Google Scholar 

  150. Ertl, H. C. and Xiang, Z. (1996) Novel vaccine approaches. J. Immunol. 156, 3579–3582.

    PubMed  CAS  Google Scholar 

  151. Descamps, V., Duffour, M. T., Mathieu, M. C., Fernandez, N., Cordier, L., Abina, M. A., et al. (1996) Strategies for cancer gene therapy using adenoviral vectors. J. Mol. Med. 74, 183–189.

    Article  PubMed  CAS  Google Scholar 

  152. Lew, D., Parker, S. E., Latimer, T., Abai, A. M., Kuwahara-Rundell, A., Doh, S. G., et al. (1995) Cancer gene therapy using plasmid DNA: pharmacokinetic study of DNA following injection in mice. Hum. Gene Ther. 6, 553–564.

    Article  PubMed  CAS  Google Scholar 

  153. Mullen, C. A. and Blaese, R. M. (1996) Gene therapy of cancer. Cancer Chemother. Biol. Response Modif. 16, 285–294.

    PubMed  CAS  Google Scholar 

  154. Parker, S. E., Vahlsing, H. L., Serfilippi, L. M., Franklin, C. L., Doh, S. G., Gromkowski, S. H., et al. (1995) Cancer gene therapy using plasmid DNA: safety evaluation in rodents and non-human primates. Hum. Gene Ther. 6, 575–590.

    Article  PubMed  CAS  Google Scholar 

  155. Ulmer, J. B., Donnelly, J. J., Parker, S. E., Rhodes, G. H., Felgner, P. L., Dwarki, V. J., et al. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745–1749.

    Article  PubMed  CAS  Google Scholar 

  156. Kohn, D. B. and Sarver, N. (1996) Gene therapy for HIV-1 infection. Adv. Exp. Med. Biol. 394, 421–428.

    PubMed  CAS  Google Scholar 

  157. Van Ginkel, F. W., Liu, C., Simecka, J. W., Dong, J. Y., Greenway, T., Frizzell, R. A., et al. (1995) Intratracheal gene delivery with adenoviral vector induces elevated systemic IgG and mucosal IgA antibodies to adenovirus and betagalactosidase. Hum. Gene Ther. 6, 895–903.

    Article  PubMed  CAS  Google Scholar 

  158. Gao, G. P., Yang, Y., and Wilson, J. M. (1996) Biology of adenovirus vectors with E1 and E4 deletions for liver-directed gene therapy. J. Virol. 70, 8934–8943.

    PubMed  CAS  Google Scholar 

  159. Yang, Y., Greenough, K., and Wilson, J. M. (1996) Transient immune blockade prevents formation of neutralizing antibody to recombinant adenovirus and allows repeated gene transfer to mouse liver. Gene Ther. 3, 412–420.

    PubMed  CAS  Google Scholar 

  160. Barr, D., Tubb, J., Ferguson, D., Scaria, A., Lieber, A., Wilson, C., Perkins, J., and Kay, M. A. (1995) Strain related variations in adenovirally mediated transgene expression from mouse hepatocytes in vivo: comparisons between immunocompetent and immunodeficient inbred strains. Gene Ther. 2, 151–155.

    PubMed  CAS  Google Scholar 

  161. Acsadi, G., Lochmuller, H., Jani, A., Huard, J., Massie, B., Prescott, S., et al. (1996) Dystrophin expression in muscles of mdx mice after adenovirus-mediated in vivo gene transfer. Hum. Gene Ther. 7, 129–140.

    Article  PubMed  CAS  Google Scholar 

  162. Yang, Y., Jooss, K. U., Su, Q., Ertl, H. C., and Wilson, J. M. (1996) Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo. Gene Ther. 3, 137–144.

    PubMed  Google Scholar 

  163. McCoy, R. D., Davidson, B. L., Roessler, B. J., Huffnagle, G. B., Janich, S. L., Laing, T. J., and Simon, R. H. (1995) Pulmonary inflammation induced by incomplete or inactivated adenoviral particles. Hum. Gene Ther. 6, 1553–1560.

    Article  PubMed  CAS  Google Scholar 

  164. Kotin, R. M. (1994) Prospects for the use of adeno-associated virus as a vector for human gene therapy. Hum. Gene Ther. 5, 793–801.

    Article  PubMed  CAS  Google Scholar 

  165. Jooss, K., Yang, Y., Fisher, K. J., and Wilson, J. M. (1998) Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J. Virol. 72, 4212–4223.

    PubMed  CAS  Google Scholar 

  166. Manning, W. C., Zhou, S., Bland, M. P., Escobedo, J. A., and Dwarki, V. (1998) Transient immunosuppression allows transgene expression following readministration of adeno associated viral vectors. Hum. Gene Ther. 9, 477–485.

    Article  PubMed  CAS  Google Scholar 

  167. Flotte, T. R., Afione, S. A., Solow, R., Drumm, M. L., Markakis, D., Guggino, W. B., Zeitlin, P. L., and Carter, B. J. (1993) Expression of the cystic fibrosis transmembrane conductance regulator from a novel adeno associated virus promoter. J. Biol. Chem. 268, 3781–3790.

    PubMed  CAS  Google Scholar 

  168. Baudard, M., Flotte, T. R., Aran, J. M., Thierry, A. R., Pastan, I., Pang, M. G., Kearns, W. G., and Gottesman, M. M. (1996) Expression of the human multidrug resistance and glucocerebrosidase cDNAs from adeno-associated vectors: efficient promoter activity of AAV sequences and in vivo delivery via liposomes. Hum. Gene Ther. 7, 1309–1322.

    Article  PubMed  CAS  Google Scholar 

  169. Chang, L. S., Shi, Y., and Shenk, T. (1989) Adeno-associated virus P5 promoter contains an adenovirus E1A-inducible element and a binding site for the major late transcription factor. J. Virol. 63, 3479–3488.

    PubMed  CAS  Google Scholar 

  170. Shi, Y., Seto, E., Chang, L. S., and Shenk, T. (1991) Transcriptional repression by YY1, a human GLI-Kruppel-related protein, and relief of repression by adenovirus E1A protein. Cell 67, 377–388.

    Article  PubMed  CAS  Google Scholar 

  171. Smale, S. T. and Baltimore, D. (1989) “Initiator” as a transcription control element. Cell 57, 103–113.

    Article  PubMed  CAS  Google Scholar 

  172. Urabe, M., Hasumi, Y., Ogasawara, Y., Matsushita, T., Kamoshita, N., Nomoto, A., et al. (1997) Novel dicistronic AAV vector using a short IRES segment derived from hepatitis C virus genome. Gene 200, 157–162.

    Article  PubMed  CAS  Google Scholar 

  173. Mizuno, M. and Yoshida, J. (1998) Improvement of transduction efficiency of recombinant adeno-associated virus vector by entrapment in multilamellar liposomes. Jpn. J. Cancer Res. 89, 352–354.

    PubMed  CAS  Google Scholar 

  174. Doll, R. F., Crandall, J. E., Dyer, C. A., Aucoin, J. M., and Smith, F. I. (1996) Comparison of promoter strengths on gene delivery into mammalian brain cells using AAV vectors. Gene Ther. 3, 437–447.

    PubMed  CAS  Google Scholar 

  175. Philip, R., Brunette, E., Kilinski, L., Murugesh, D., McNally, M. A., Ucar, K., et al. (1994) Efficient and sustained gene expression in primary T lymphocytes and primary and cultured tumor cells mediated by adeno-associated virusplasmid DNA complexed to cationic liposomes. Mol. Cell Biol. 14, 2411–2418.

    PubMed  CAS  Google Scholar 

  176. Fu, Y., Wang, Y., and Evans, S. M. (1998) Viral sequences enable efficient and tissue-specific expression of transgenes in Xenopus. Nat. Biotechnol. 16, 253–257.

    Article  CAS  Google Scholar 

  177. Fisher, K. J., Kelley, W. M., Burda, J. F., and Wilson, J. M. (1996) Novel adenovirus-adeno-associated virus hybrid vector that displays efficient rescue and delivery of the AAV genome. Hum. Gene Ther. 7, 2079–2087.

    Article  PubMed  CAS  Google Scholar 

  178. Flotte, T. R. and Carter, B. J. (1997) In vivo gene therapy with adeno-associated virus vectors for cystic fibrosis. Adv. Pharmacol. 40, 85–101.

    Article  PubMed  CAS  Google Scholar 

  179. Johnston, K. M., Jacoby, D., Pechan, P. A., Fraefel, C., Borghesani, P., Schuback, D., et al. (1997) HSV/AAV hybrid amplicon vectors extend transgene expression in human glioma cells. Hum. Gene Ther. 8, 359–370.

    Article  PubMed  CAS  Google Scholar 

  180. Fraefel, C., Jacoby, D. R., Lage, C., Hilderbrand, H., Chou, J. Y., Alt, F. W., Breakefield, X. O., and Majzoub, J. A. (1997) Gene transfer into hepatocytes mediated by helper virus-free HSV/AAV hybrid vectors. Mol. Med. 3, 813–825.

    PubMed  CAS  Google Scholar 

  181. Palombo, F., Monciotti, A., Recchia, A., Cortese, R., Ciliberto, G., and La Monica, N. (1998) Site-specific integration in mammalian cells mediated by a new hybrid baculovirus-adeno associated virus vector. J. Virol. 72, 5025–5034.

    PubMed  CAS  Google Scholar 

  182. Miller, J. L., Donahue, R. E., Sellers, S. E., Samulski, R. J., Young, N. S., and Nienhuis, A. W. (1994) Recombinant adeno-associated virus (rAAV)-mediated expression of a human gamma-globin gene in human progenitor-derived erythroid cells. Proc. Natl. Acad. Sci. USA 91, 10,183–10,187.

    Article  PubMed  CAS  Google Scholar 

  183. Ponnazhagan, S., Mukherjee, P., Wang, X. S., Qing, K., Kube, D. M., Mah, C., et al. (1997) Adeno-associated virus type 2-mediated transduction in primary human bone marrow-derived CD34+ hematopoietic progenitor cells: donor variation and correlation of transgene expression with cellular differentiation. J. Virol. 71, 8262–2867.

    PubMed  CAS  Google Scholar 

  184. Walsh, C. E., Nienhuis, A. W., Samulski, R. J., Brown, M. G., Miller, J. L., Young, N. S., and Liu, J. M. (1994) Phenotypic correction of Fanconi anemia in human hematopoietic cells with a recombinant adeno associated virus vector. J. Clin. Invest. 94, 1440–1448.

    Article  PubMed  CAS  Google Scholar 

  185. Blau, H. M. and Springer, M. L. (1995) Muscle-mediated gene therapy. N. Engl. J. Med. 333, 1554–1556.

    Article  PubMed  CAS  Google Scholar 

  186. Miller, J. B. and Boyce, F. M. (1995) Gene therapy by and for muscle cells. Trends Genet. 11, 163–165.

    Article  PubMed  CAS  Google Scholar 

  187. Xing, Z., Ohkawara, Y., Jordana, M., Graham, F. L., and Gauldie, J. (1997) Adenoviral vector-mediated interleukin-10 expression in vivo: intramuscular gene transfer inhibits cytokin responses in endotoxemia. Gene Ther. 4, 140–149.

    Article  PubMed  CAS  Google Scholar 

  188. Miller, G., Steinbrecher, R. A., Murdock, P. J., Tuddenham, E. G., Lee, C. A., Pasi, K. J., and Goldspink, G. (1995) Expression of factor VII by muscle cells in vitro and in vivo following direct gene transfer: modelling gene therapy for haemophilia. Gene Ther. 2, 736–742.

    PubMed  CAS  Google Scholar 

  189. 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, 5951–59

    PubMed  CAS  Google Scholar 

  190. Huard, J., Lochmuller, H., Acsadi, G., Jani, A., Holland, P., Guerin, C., Massie, B., and Karpati, G. (1995) Differential short-term transduction efficiency of adult versus newborn mouse tissues by adenoviral recombinants. Exp. Mol. Pathol. 62, 131-143.

    Google Scholar 

  191. Snyder, R. O., Spratt, S. K., Lagarde, C., Bohl, D., Kaspar, B., Sloan, B., Cohen, L. K., and Danos, O. (1997) Efficient and stable adeno-associated virus-mediated transduction in the skeletal muscle of adult immunocompetent mice. Hum. Gene Ther. 8, 1891–1900

    Article  PubMed  CAS  Google Scholar 

  192. Kaplitt, M. G., Xiao, X., Samulski, R. J., Li, J., Ojamaa, K., Klein, I. L., et al. (1996) Long-term gene transfer in porcine myocardium after coronary infusion of an adeno-associated virus vector. Ann. Thorac. Surg. 62, 1669–1676.

    Article  PubMed  CAS  Google Scholar 

  193. Rolling, F., Nong, Z., Pisvin, S., and Collen, D. (1997) Adeno-associated virusmediated gene transfer into rat carotid arteries. Gene Ther. 4, 757–761.

    Article  PubMed  CAS  Google Scholar 

  194. Maeda, Y., Ikeda, U., Ogasawara, Y., Urabe, M., Takizawa, T., Saito, T., Colosi, P., Kurtzman, G., Shimada, K., and Ozawa, K. (1997) Gene transfer into vascular cells using adeno-associated virus (AAV) vectors. Cardiovasc. Res. 35, 514–521.

    Article  PubMed  CAS  Google Scholar 

  195. Halbert, C. L., Alexander, I. E., Wolgamot, G. M., and Miller, A. D. (1995) Adeno-associated virus vectors transduce primary cells much less efficiently than immortalized cells. J. Virol. 69, 1473–14

    PubMed  CAS  Google Scholar 

  196. Brange, J., Hallund, O., and Sorensen, E. (1992) Chemical stability of insulin. Isolation, charac-terization and identification of insulin transformation products. Acta Pharm. Nord. 4, 223–232.

    PubMed  CAS  Google Scholar 

  197. Kuo, W. L. and Montag, A. G., Rosner, M. R. (1993) Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues. Endocrinology 132, 604S–611S.

    Article  Google Scholar 

  198. Kaufmann, J. E., Irminger, J. C., Mungall, J., Halban, P. A. (1997) Proinsulin conversion in GH3 cells after coexpression of human proinsulin with the endoproteases PC2 and/or PC3. Diabetes 46, 978–82.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Richard J. Bartlett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jesica M. McCue
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Delaware, Newark, Delaware

    Eric B. Kmiec

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Humana Press Inc.

About this protocol

Cite this protocol

Bartlett, R.J., McCue, J.M. (2000). Adeno-Associated Virus Based Gene Therapy in Skeletal Muscle. In: Kmiec, E.B. (eds) Gene Targeting Protocols. Methods in Molecular Biology™, vol 133. Humana Press. https://doi.org/10.1385/1-59259-215-5:127

Download citation

  • DOI: https://doi.org/10.1385/1-59259-215-5:127

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-360-3

  • Online ISBN: 978-1-59259-215-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation