Xiao Xiao, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Published online: June 2001
DOI: 10.1038/npg.els.0000408
Adeno-associated viruses are small, nonenveloped, single-stranded viruses of the genus Dependovirus, family Parvoviridae. They are so named because their propagation depends upon the coinfection by an unrelated virus for essential helper functions.
Keywords: parvoviridae; AAV; episomal persistence; recombinant viral vector; vector production; gene therapy; rep proteins; hairpin transfer replication; site-specific integration
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Figure 1. Electron microscopy of (a) adeno-associated virus 2 (AAV2) and (b) its helper virus, adenovirus 2. Note the few empty AAV particles that lack viral DNA genome and are imaged like a ring.
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Figure 2. The genome structure and gene products of adeno-associated virus 2 (AAV2). ITR, inverted terminal repeat.
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Figure 3. The latent and productive life cycles of adeno-associated virus (AAV). Ad, adenovirus.
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Figure 4. The terminal transfer model of linear adeno-associated virus (AAV) DNA replication. The 3¢ termini are indicated by an arrowhead, and newly synthesized DNA by dotted lines.
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Figure 5. Adeno-associated virus (AAV) vector production by the helper virus-free, triple-plasmid transfection method, where no adenovirus is used nor can it be generated. Three of the five essential adenovirus (Ad) helper genes are provided by the helper plasmid (VA RNA, E2 and E4), while the other two genes (E1A and E1B) are provided by the host 293 cells. ITR, inverted terminal repeat.
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Figure 6. Efficient and long-term gene transfer into mature muscle after direct injection of an adeno-associated virus (AAV) vector that contains a -galactosidase gene from Escherichia coli. Transverse thin section of the vector-injected mouse muscle showed blue-coloured muscle cells across the entire area after X-gal staining, which turned the -galactosidase-positive cells blue. Magnification 40×.
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| Kotin RM, Siniscalco M, Samulski RJ et al. (1990) Site-specific integration by adeno-associated virus. Proceedings of the National Academy of Sciences of the United States of America 87: 2211–2215. | |
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| Samulski RJ, Chang LS and Shenk T (1989) Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. Journal of Virology 63: 3822–3828. | |
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| Smith RH and Kotin RM (1998) The Rep52 gene product of adeno-associated virus is a DNA helicase with 3¢ to 5¢ polarity. Journal of Virology 72: 4874–4881. | |
| Summerford C and Samulski RJ (1998) Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. Journal of Virology 72: 1438–1445. | |
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| Xiao X, Li J and Samulski RJ (1998) Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. Journal of Virology 72: 2224–2232. | |
| Xiao X, Li J and Samulski RJ (1996) Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. Journal of Virology 70: 8098–8108. | |
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| Further Reading | |
| Berns KI and Giraud C (1996) Biology of adeno-associated virus. Current Topics in Microbiology and Immunology 218: 1–23. | |
| Muzyczka N (1992) Use of adeno-associated virus as a general transduction vector for mammalian cells. Current Topics in Microbiology and Immunology 158: 97–129. | |
| book Samulski RJ, Sally M and Muzyczka N (1999) "Adeno-associated viral vectors". In: Friedmann T (ed.) Development of Human Gene Therapy, pp. 131–172. Cold Spring Harbor: Cold Spring Harbor Laboratory Press. | |
| book Tijssen P (ed.) (1990) Handbook of Parvoviruses. Boca Raton, FL: CRC Press. | |
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