Advertisement

Methods for Adeno-Associated Virus-Mediated Gene Transfer into Muscle

  • Terry J. Amiss
  • Richard Jude Samulski
Part of the Methods in Molecular Biology™ book series (MIMB, volume 175)

Abstract

Gene therapy vectors based on adeno-associated virus (AAV) are being used to successfully transduce a number of different tissues, including muscle (1). The first demonstration of muscle transduction by recombinant AAV (rAAV) was reported by Xiao et al. (2) in 1996. In that report, LacZ expression from an AAV vector was established in immunocompetent mice for over 1.5 yr. Since that time, several laboratories have confirmed these observations with direct im injection of rAAV followed by sustained expression of various transgenes such as α-glucuronidase, alpha-1-antitrypsin, erythropoietin, and coagulation factor IX (3–6). Unlike other viral vectors, AAV appears to avoid immune response to the vector transgene, and, therefore, efforts to evaluate this delivery system for human use through testing large animal models have been initiated. Although the initial observations were hailed with success, in 1998 Monohan et al. (6) established that trace amounts of adenovirus helper elicit a cellular immune response to the AAV-transduced tissue. Critical to the success of long-term vector expression is the quality of the AAV virus. Soon after this observation, efforts were made to improve the procedure for generating rAAV vectors (7,8). In this chapter, we describe how to produce rAAV free of wild-type adenovirus. In addition, Summerford and Samulski (9) recently identified the receptor for AAV, heparan sulfate proteoglycan.

Keywords

Recombinant Virus Saline Sodium Citrate Gene Therapy Vector rAAV Vector Church Buffer 
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.

References

  1. 1.
    Samulski, R. J., Sally, M., and Muzyczka, N. (1999) Adeno-associated viral vectors, in The Development of Human Gene Therapy (Friedmann, T. ed.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 131–172.Google Scholar
  2. 2.
    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. 11, 8098–8108.Google Scholar
  3. 3.
    Daly, T. M., Okuyama, T., Vogler, C., Haskins, M. E., Muzyczka, N., and Sands, M. S. (1999) Neonatal intramusuclar injection with recombinant adeno-associated virus results in prolonged beta-glucuronidase expression in situ and correction of liver pathology in mucopolysaccharidosis in type VII mice. Hum. Gene Ther. 10, 85–94.PubMedCrossRefGoogle Scholar
  4. 4.
    Song S., Morgan, M., Ellis, T., Poirier, A., Chesnut, K., Wang, J., Brantly, M., Muzyzcka, N., Byrne, B. J., Atkinson, M., and Flotte, T. R. (1998) Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc. Natl. Acad. Sci. USA 95, 14,384–14,388.PubMedCrossRefGoogle Scholar
  5. 5.
    Bohl, D., Salvetti, A., Moullier, P., and Heard, J. M. (1998) Control of erythropoietin delivery by doxycycline in mice after intramuscular injection of adeno-associated vector. Blood 92, 1512–1517.PubMedGoogle Scholar
  6. 6.
    Monahan, P. E., Samulski, R. J., Tazelaar, J., Xiao, X., Nichols, T. C., Bellinger, D. A., and Read, M. S. (1998) Direct intramuscular injection with recombinant AAV vectors results in sustained expression in a dog model of hemophilia Gene Ther. 5, 40–49.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedGoogle Scholar
  8. 8.
    Ferrari, F. K., Xiao, X., McCarty, D., and Samulski, R. J. (1997) New developments in the generation of Ad-free, high-titer rAAV gene therapy vectors. Nature Med. 3, 1295, 1296.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedGoogle Scholar
  10. 10.
    Summerford C. and Samulski, R. J. (1999) Viral receptors and vector purification: new approaches for generating clinical-grade reagents. Nature Med. 5, 587, 588.PubMedCrossRefGoogle Scholar
  11. 11.
    Zolotukhin, S., Byrne, B. J., Mason, E., Zolotuknin, I., Potter, M., Chesnut, K., Summerford, C., Samulski, R. J., and Muzyczka, N. (1999) Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther. 6, 973–985.PubMedCrossRefGoogle Scholar
  12. 12.
    Parks, W. P., Melnick, J. L., Rongey, R., and Mayor, H. D. (1967) Physical assay and growth cycle studies of a defective adeno-satellite virus. J. Virol. 1, 171–180.PubMedGoogle Scholar
  13. 13.
    Atchinson, R. W., Casto, B. C., and Hammond, W. M. (1965) Adenovirus-associated defective virus particles. Science 149, 754–756.CrossRefGoogle Scholar
  14. 14.
    Hoggan, M. D., Blacklow, N. R., and Row, W. P. (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc. Natl. Acad. Sci. USA 55, 1457–1471.CrossRefGoogle Scholar
  15. 15.
    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.PubMedGoogle Scholar
  16. 16.
    Samulski, R. J. (1993) Adeno-associated virus: integration at a specific chromosomal location. Curr. Opin. Gen. Dev. 3, 74–80.CrossRefGoogle Scholar
  17. 17.
    Kotin, R. M., Siniscalco, M., Samulski, R. J., Zhu, X., Hunter, L., Laughlin, C. A., McLaughlin, S., Muzyczka, N., Rocchi, M., and Berns, K. L. (1990) Site-specific integration by adeno-assoicated virus. Proc. Natl. Acad. Sci. USA 87, 2211–2215.PubMedCrossRefGoogle Scholar
  18. 18.
    Kotin, R. M., Linden, R. M., and Berns, K. I. (1992) Characterization of a preferred site on human chromosome l 9q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO J. 11, 5071–5078.PubMedGoogle Scholar
  19. 19.
    Xiao X., Xiao, W., Li, J., and Samulski, R. J. (1997) A novel 165-base-pair termina repeat sequence is the sole cis requirement for the adeno-associated virus life cycle. J. Virol. 71, 941–948.PubMedGoogle Scholar
  20. 20.
    Berns, K. I. and Giraud, C. (1995) Adeno-associated virus (AAV) vectors in gene therapy. Curr. Topics Microbiol. Immun. 218, 1–25.Google Scholar
  21. 21.
    Bartlett, J. S. and Samulski, R. J. (1996) Production of recombinant adeno-associated viral vectors, in Current Protocols in Human Genetics, John Wiley & Sons, Philadelphia, pp. 12.1.1–12.1.24.Google Scholar
  22. 22.
    ShiLman, M. I. and Stern, D. G. (1995) A reliable and sensitive method for non-radioactive northern blot analysis of nerve growth factor mRNA from brain tissues. J. Neurosci. Methods 59, 205–208.CrossRefGoogle Scholar
  23. 23.
    Yang, C. C., Xiao, X., Zhu, X., Ansardi, D. C., Epstein, N. C., Frey, M. R., Matera, A. G., and Samulski, R. J. (1997) Cellular recombination pathways and viral terminal repeat hairpin structures are sufficient for adeno-associated virus integration in vivo and in vitro. J. Virol. 71, 9231–9247.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2001

Authors and Affiliations

  • Terry J. Amiss
    • 1
  • Richard Jude Samulski
    • 1
  1. 1.Gene Therapy CenterUniversity of North Carolina at Chapel HillChapel Hill

Personalised recommendations