Skip to main content
SpringerLink
Log in

Packaging Systems for Adeno-associated Virus Vectors

  • Chapter
Adeno-Associated Virus (AAV) Vectors in Gene Therapy

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 218))

Abstract

The promise and hopes that gene therapy vectors derived from adeno-associated virus (AAV) will make the leap from the laboratory bench to the clinic bedside are thoroughly described in this volume of Current Topics of Microbiology and Immunology. As more investigators enter this rapidly growing field, AAV’s ability to deliver genes of therapeutic potential will be explored for many acquired and hereditary diseases. AAV has several characteristics that make it an appealing human gene therapy vector: (1) the virus is naturally defective in that it requires the help of a coinfecting virus, usually adenovirus, for it to efficiently complete its life cycle, (2) in the absence of helper virus infection, AAV establishes a lysogenic state, usually in a site-specific locus on chromosome 19, (3) AAV is nonpathogenic because it has not been implicated as the causative agent of any known disease, (4) AAV’s small DNA genome (4680 nucleotides) allows for easy manipulation by standard recombinant DNA methodology. These characteristics have been described in other chapters of this volume but are briefly summarized here.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alwine JC (1985) Transient gene expression control: effects of transfected DNA stability and trans-activation by viral early proteins. Mol Cell Biol 5: 1034–1042

    PubMed  CAS  Google Scholar 

  • Antoni BA, Rabson AB, Miller IL, Trempe JP, Chejanovsky N, Carter BJ (1991) Adeno-associated virus rep protein inhibits human immunodeficiency virus type 1 production in human cells. J Virol 65: 396–404

    PubMed  CAS  Google Scholar 

  • Bantel-Schaal U, zur Hausen H (1988) Adeno-associated viruses inhibit SV40 DNA amplification and replication of herpes simplex virus in SV40-transformed hamster cells. Virology 164: 64–74

    Article  PubMed  CAS  Google Scholar 

  • Batchu RB, Kotin RM, Hermonat PL (1994) The regulatory rep protein of adeno-associated virus binds to sequences within the c-H-ras promoter. Cancer Lett 86: 23–31

    Article  PubMed  CAS  Google Scholar 

  • Beaton A, Palumbo P, Berns KI (1989) Expression of the AAV p5 and p19 promoters is negatively regulated in trans by the rep protein. J Virol 63: 4450–4454

    PubMed  CAS  Google Scholar 

  • Becerra SP, Koczot F, Fabisch P, Rose JA (1988) Synthesis of adeno-associated virus structural proteins requires both alternative mRNA splicing and alternative initiations from a single transcript. J Virol 62: 2745–2754

    PubMed  CAS  Google Scholar 

  • Berkner KL (1992) Expression of heterologous sequences in adenoviral vectors. In: Muzyczka N (ed) Viral expression vectors. Springer, Berlin Heidelberg New York, pp 39–66 (Current topics in microbiology and immunology, vol 158)

    Chapter  Google Scholar 

  • Berns KI (1990) Parvoviridae and their replication: In: Fields BN, Knipe DM (eds) Virology, vol 2, 2nd edn. Raven, New York, pp 1743–1763

    Google Scholar 

  • Bohinski RJ, Huffman JA, Whitsett JA, Lattier DL (1993) Cis-active elements controlling lung-specific expression of human pulmonary surfactant protein B genes. J Biol Chem 268: 11160–11166

    PubMed  CAS  Google Scholar 

  • Carter BJ, Laughlin CA, delaMaza LM, Myers M (1979) Adeno-associated virus autointerference. Virology 92: 449–462

    Article  PubMed  CAS  Google Scholar 

  • Chejanovsky N, Carter BJ (1989) Mutagenesis of an AUG codon in the adeno-associated virus rep gene: effects on viral DNA replication. Virology 173: 120–128

    Article  PubMed  CAS  Google Scholar 

  • Chiorini JA, Weitzman MD, Owens RA, Urcelay E, Safer B, Kotin RM (1994) Biologically active rep proteins of adeno-associated virus type 2 produced as fusion proteins in Escherichia coli. J Virol 68: 797–804

    PubMed  CAS  Google Scholar 

  • Curiel DT, Agarwal S, Wagner E, Cotten M (1991) Adenovirus enhancement of transferrin-polylysine-mediated gene delivery. Proc Natl Acad Sci USA 88: 8850–8854

    Article  PubMed  CAS  Google Scholar 

  • delaMaza LM, Carter BJ (1978) DNA structure of incomplete adeno-associated virus particles. In: Ward DC, Tattersall P (eds) Replication of mammalian parvoviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp 193–204

    Google Scholar 

  • Fisher KJ, Wilson JM (1994) Biochemical and functional analysis of an adenovirus-based ligand complex for gene transfer. Biochem J 299: 49–58

    PubMed  CAS  Google Scholar 

  • Flotte TR, Afione SA, Solow R, Drumm ML, Markakis D, Guggino WB, Zeitlin PL, Carter BJ (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 

  • Georg-Fries B, Biederlack S, Wolf J, zur Hausen H (1984) Analysis of helper dependence, and seroepidemiology of a new human parvovirus. Virology 134: 64–71

    Article  PubMed  CAS  Google Scholar 

  • Goodman S, Xiao X, Donahue RE, Moulton A, Miller J, Walsh C, Young NS, Samulski RJ, Nienhuis AW (1994) Recombinant adeno-associated virus mediated gene transfer into hematopoietic progenitor cells. Blood 84: 1492–1500

    PubMed  CAS  Google Scholar 

  • Graham FL, Smiley J, Russell WC, Naiva R (1977) Characteristics of a human cell line transformed by DNA from adenovirus type 5. J Gen Virol 36: 59–72

    Article  PubMed  CAS  Google Scholar 

  • Heibronn R, Bürkle A, Stephan S, and zur Hausen (1990) The adeno-associated virus rep gene suppresses herpes simplex virus-induced DNA amplification. J Virol 64: 3012–3018

    Google Scholar 

  • Hermonat PL (1989) The adeno-associated virus rep78 gene inhibits cellular transformation by bovine papillomavirus. Virology 172: 253–261

    Article  PubMed  CAS  Google Scholar 

  • Hermonat PL (1991) Inhibition of H-ras expression by the adeno-associated virus rep78 transformation suppressor gene product. Cancer Res 51: 3373–3377

    PubMed  CAS  Google Scholar 

  • Hermonat PL (1992) Inhibition of bovine papillomavirus plasmid DNA replication by adeno-associated virus. Virology 189: 329–333

    Article  PubMed  CAS  Google Scholar 

  • Hermonat PL (1994) Down-regulation of the human c-fos and c-myc proto-oncogene promoters by adeno-associated virus Rep78. Cancer Lett 81: 129–136

    Article  PubMed  CAS  Google Scholar 

  • Hermonat PL, Muzyczka N (1984) Use of adeno-associated virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue culture cells. Proc Natl Acad Sci USA 81: 6466–6470

    Article  PubMed  CAS  Google Scholar 

  • Hermonat PL, Labow MA, Wright R, Berns KI, Muzyczka N (1984) Genetics of adeno-associated virus: isolation and preliminary characterization of mutants of adeno-associated virus type 2. J Virol 51: 329–339

    PubMed  CAS  Google Scholar 

  • Hölscher C, Horker M, Kleinschmidt JA, Zentgraf H, Burkle A, Heilbronn R (1994) Cell lines inducibly expressing the adeno-associated virus (AAV) rep gene: requirements for productive replication of rep-negative AAV mutants. J Virol 68: 7169–7177

    PubMed  Google Scholar 

  • Khleif SN, Myers T, Carter BJ, Trempe JP (1991) Inhibition of cellular transformation by the adeno-associated virus rep gene. Virology 181: 738–741

    Article  PubMed  CAS  Google Scholar 

  • Kotin RM (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 

  • Kung H-J Boerkoel, Carter TH (1991) Retroviral mutagenesis of cellular oncogenes: a review with insights into the mechanisms of insertional activation. In: Kung HJ, Vogt PK (eds) Retroviral insertional mutagenesis and oncogene activation. Springer, Berlin Heidelberg New York, pp 1–24 (Current topics in microbiology and immunology, vol 171)

    Chapter  Google Scholar 

  • Kyöstiö SR, Owens RA, Weitzman MD, Antoni BA, Chejanovsky N, Carter BJ (1994) Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 NA levels. J Virol 68: 2947–2957

    PubMed  Google Scholar 

  • Labow MA, Graf LH, Berns KI (1987) Adeno-associated virus gene expression inhibits cellular transformation by heterologous genes. Mol Cell Biol 7: 1320–1325

    PubMed  CAS  Google Scholar 

  • Labow MA, Berns KI (1988) The adeno-associated virus rep gene inhibits replication of an adeno-associated virus/simian virus 40 hybrid genome in cos-7 cells. Mol Cell Biol 7: 1320–1325

    Google Scholar 

  • Lebkowski JS, Mally MA, Okarma TB, Lerch LB (1988) Adeno-associated virus: A vector system for efficient introduction and integration of DNA into a variety of mammalian cells. Mol Cell Biol 8: 3988–3996

    PubMed  CAS  Google Scholar 

  • Mayor HD, Drake S, Stahmann J, Mumford DM (1976) Antibodies to adeno-associated satellite virus and herpes simplex in sera from cancer patients and normal adults. Am J Obstet Gynecol 126: 100–104

    PubMed  CAS  Google Scholar 

  • McLaughlin SK, Collis P, Hermonat PL, Muzyczka N (1988) Adeno-associated virus general transduction vectors: analysis of proviral structures. J Virol 62: 1963–1973

    PubMed  CAS  Google Scholar 

  • Mendelson E, Miller IL, Carter BJ (1988a) Expression and rescue of a nonselected marker from an integrated AAV vector. Virology 166: 154–165

    Article  PubMed  CAS  Google Scholar 

  • Mendelson E, Smith MG, Miller IL, Carter BJ (1988b) Effect of a viral rep gene on transformation of cells by an adeno-associated virus vector. Virology 166: 612–615

    Article  PubMed  CAS  Google Scholar 

  • Miller JL, Donahue RE, Sellers SE, Samulski RJ, Young NS, Nienhuis AW (1994) Recombinant adeno-associated virus (AV)-mediated expression of a human g-globin gene in human progenitorderived erythroid cells. Pro Natl Acad Sci USA 91: 10183–10187

    Article  CAS  Google Scholar 

  • Morgan RA, Anderson WF (1993) Human gene therapy. Annu Rev Biochem 63: 191–217

    Article  Google Scholar 

  • Muzyczka N (1992) Use of adeno-associated virus as a general transduction vector for mammalian cells. In: Muzyczka N (ed) Viral expressions vectors. Springer, Berlin Heidelberg New York, pp 97–129 (Current topics in microbiology and immunology, vol 158)

    Chapter  Google Scholar 

  • Myers MW, Carter BJ (1980) Assembly of adeno-associated virus. Virology 102: 71–82

    Article  PubMed  CAS  Google Scholar 

  • Ni T-H, Zhou X, Marty DM, Zolotukhin I, Muzyczka N (1994) In vitro replication of adeno-associated virus DNA. J Virol 68: 1128–1138

    PubMed  CAS  Google Scholar 

  • Owens RA, Trempe JP, Chejanovsky N, Carter BJ (1991) Adeno-associated virus rep proteins produced in insect and mammalian expression systems: wild-type and dominant-negative mutant proteins bind to the viral replication origin. Virology 184: 14–22

    Article  PubMed  CAS  Google Scholar 

  • Parks WP, Boucher DW, Melnick JL, Taber LH, Yow MD (1970) Seroepidemiological and ecological studies of the adenovirus-associated satellite viruses. Infect Immun 2: 716–722

    PubMed  CAS  Google Scholar 

  • Ruffing M, Zentgraf H, Kleinschmidt JA (1992) Assembly of virus-like particles by recombinant structural proteins of adeno-associated virus type 2 in insect cells. J Virol 66: 6922–6930

    PubMed  CAS  Google Scholar 

  • Russell DW, Miller AD, Alexander IE (1994) Adeno-associated virus vectors preferentially transduce cells in S-phase. Proc Natl Acad Sci USA 91: 8915–8919

    Article  PubMed  CAS  Google Scholar 

  • Samulski RJ (1993) Adeno-associated virus: integration at a specific chromosomal locus. Curr Opin Genet Devel 3: 74–80

    Article  CAS  Google Scholar 

  • Samulski RJ, Chang L-S, Shenk T (1987) A recombinant plasmid from which an infectious adeno-associated virus genome can be excised in vitro and its use to study viral replication. J Virol 61: 3096–3011

    PubMed  CAS  Google Scholar 

  • Samulski RJ, Chang L-S, 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 

  • Samulski RJ, Xiao X, Kaplitt M, Leone Pfaff P, O’Malley K, During M (1994) Generation of AAV vectors for transduction and expression in neuronal cells in vivo. Gene therapy 21–25 Sept 1994, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (abstract)

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Srivastava A, Lusby EW, Berns KI (1983) Nucleotide sequence and organization of the adeno-associated virus 2 genome. J Virol 45: 555–564

    PubMed  CAS  Google Scholar 

  • Thomson BJ, Weindler FW, Gray D, Schwaab V, Heilbronn R (1994) Human herpesvirus 6 (HHV-6) is a helper virus for adeno-associated virus type 2 (AAV-2) and the AAV-2 rep gene homologue in HHV-6 can mediate AAV-2 DNA replication and regulate gene expression. Virology 204: 304–311

    Article  PubMed  CAS  Google Scholar 

  • Tobiasch E, Rabreau M, Geletneky K, Larue-Charlus S, Severin F, Becker N, Schlehofer JR (1994) Detection of adeno-associated virus DNA in human genital tissue and in material from spontaneous abortion. J Med Virol 44: 215–222

    Article  PubMed  CAS  Google Scholar 

  • Tratschin J-D, Miller IL, Carter BJ (1984a) Genetic analysis of adeno-associated virus: Property of deletion mutants constructed in vitro and evidence for an adeno-associated virus replication function. J Virol 51: 611–619

    PubMed  CAS  Google Scholar 

  • Tratschin J-D, West MH, Sandbank T, Carter BJ (1984b) A human parvovirus, adeno-associated virus, as a eukaryotic vector: transient expression and encapsidation of the prokaryotic gene for chloramphenicol acetyltransferase. Mol Cell Biol 4: 2072–2081

    PubMed  CAS  Google Scholar 

  • Tratschin J-D, Miller IL, Smith MG, Carter BJ (1985) Adeno-associated virus vector for high-frequency integration, expression, and rescue of genes in mammalian cells. Mol Cell Biol 5: 3251–3260.

    PubMed  CAS  Google Scholar 

  • Tratschin J-D, Tal J, Carter BJ (1986) Negative and positive regulation intraris of gene expression from adeno-associated virus vectors in mammalian cells by a viral rep gene product. Mol Cell Biol 6: 2884–2894

    PubMed  CAS  Google Scholar 

  • Trempe JP, Carter BJ (1988) Regulation of adeno-associated virus gene expression in 293 cells: Control of NA abundance and translation. J Virol 62: 68–74

    PubMed  CAS  Google Scholar 

  • Vincent KA, Moore GK, Haigwood NI(1990) Replication and packaging of HIV envelope genes in a novel adeno-associated virus vector system. Vaccines 90: 350–353

    Google Scholar 

  • Wagner E, Zatloukal K, Cotten M, Kirlappos H, Mechtler K, Curiel DT, Birnstiel M (1992) Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc Natl Acad Sci USA 89: 6099–6103

    Article  PubMed  CAS  Google Scholar 

  • Winocour E, Callaham MF, Huberman E (1988) Perturbation of the cell cycle by adeno-associated virus. Virology 167: 393–399

    PubMed  CAS  Google Scholar 

  • Yakobson B, Koch T, Winocour E (1987) Replication of adeno-associated virus in synchronized cells without the addition of a helper virus. J Virol 61: 972–981

    PubMed  CAS  Google Scholar 

  • Yakobson B, Hrynko T, Peak MJ, Winocour E (1989) Replication of adeno-associated virus in cells irradiated with UV light at 254 nm. J Virol 63: 1023–1230

    PubMed  CAS  Google Scholar 

  • Yalkinoglu AO, Heilbronn R, Burkle A, Schlehofer JR, zur Hausen H (1988) DNA amplification of adeno-associated virus as a response to cellular genotoxic stress. Cancer Res 48: 3123–3125

    PubMed  CAS  Google Scholar 

  • Yang Q, Chen F, Trempe JP (1994) Characterization of cell lines that inducibly express the adeno-associated virus Rep proteins. J Virol 68: 4847–4856

    PubMed  CAS  Google Scholar 

  • Yang Q, Chen F, Ross J, Trempe JP (1995) Inhibition of Cellular and SV40 DNA Replication by the adeno-associated Virus Rep Proteins. Virology (in press)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical College of Ohio, P.O. Box 10008, 43699, Toledo, OH, USA

    J. P. Trempe

Authors
  1. J. P. Trempe
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Hearst Microbiology Research Center, Department of Microbiology, Cornell University Medical College, 1300 York Avenue, Box 62, 10021, New York, NY, USA

    Kenneth I. Berns M.D., Ph.D.  & Catherine Giraud Ph.D.  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Trempe, J.P. (1996). Packaging Systems for Adeno-associated Virus Vectors. In: Berns, K.I., Giraud, C. (eds) Adeno-Associated Virus (AAV) Vectors in Gene Therapy. Current Topics in Microbiology and Immunology, vol 218. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80207-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-80207-2_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-80209-6

  • Online ISBN: 978-3-642-80207-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation