Abstract
Adeno-associated Virus (AAV) is classified as a member of the family Parvoviridae (Siegl et al. 1985; Berns 1990a). Members are small, nonenveloped, icosahedral viruses (diameter ca. 20–26 nm) with linear, single-stranded DNA genomes of 4.7–6 kb. Parvoviridae have been isolated from many species ranging from insects to humans. AAV is assigned to the genus Dependovirus, so named because the virus was discovered as a contaminant in purified adenovirus (Ad) stocks and in most instances does not productively infect cells in culture unless there is a coinfection by an unrelated helper virus, which is most commonly Ad, but also can be any type of herpesvirus (Atchinson et al. 1965; Hoggan et al. 1966; Buller et al. 1981). Various serotypes have been isolated from birds and many mammalian species, including humans. About 90% of U.S. adults are seropositive, but in no case has the virus been implicated as the etiological agent for a human disease or as the cause of disease in any other species. Because of the requirement for a helper coinfection for productive infection in cell culture, AAV was long considered to be a defective virus. Detailed studies described below have demonstrated that the virus is not defective, but rather preferentially establishes a latent infection in a healthy cell and is only induced to undergo productive vegetative multiplication when the host cell is stressed.
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References
Atchinson RW, Casto BC, Hammond WM (1965) Adenovirus-associated defective virus particles. Science 149: 754–756
Bantel-Schaal U (1991) Infection with adeno-associated parvovirus leads to increased sensitivity of mammalian cells to stress. Virology 182: 260–268
Bantel-Schaal U, Stöhr M (1992) Influence of adeno-associated virus on adherence and growth properties of normal cells. J Virol 66: 773–779
Beaton A, Palumbo P, Berns Kl (1989) Expression from the adeno-associated virus p5 and p19 promoters is negatively regulated in trans by the rep protein. J Virol 63: 4450–4454
Becerra SP, Koczot F, Fabisch P, Rose JA (1988) Synthesis of adeno-associated virus structural proteins requires both alternative mRNA splicing and alternative initiations form a single transcript. J Virol 62: 2745–2754
Berns KI (1990a) Parvoviridae and their replication. In: Fields BN, Knipe DM (eds) Virology, vol 2, 2nd edn. Raven, New York, pp 1743–1763
Berns KI (1990b) Parvovirus replication. Mircobiol Rev 54: 316–329
Berns KI, Linden RM (1995) The cryptic life cycle of adeno-associated virus. Bioessays 17: 237–245
Berns KI, Pinkerton TC, Thomas GF, Hoggan MD (1975) Detection of adeno-associated virus (AAV) specific nucleotide sequences in DNA isolated from latently infected Detroit 6 cells. Virology 68: 556–560
Berns KI, Kotin RM, Labow MA (1988) Regulation of adeno-associated virus DNA replication. Biochem Biophys Acta 951: 425–429
Bohenzky RA, Le Febvre RB, Berns KI (1988) Sequence and symmetry requirements within the internal palindromic sequences of the adeno-associated virus terminal repeat. Virology 166: 316–327
Buller RM, Janik JE, Sebring ED, Rose JA (1981) Herpes simplex virus type 1 and 2 completely help adeno-associated virus replication. J Virol 40: 241–247
Carter BJ (1992) Adeno-associated virus vectors. Curr Opin Biotechnol 3: 533–539
Cassinotti P, Weitz M, Tratschin JD (1988) Organization of the adeno-associated virus (AAV) capsid gene: mapping of a minor spliced mRNA coding for virus capsid protein 1. Virology 167: 176–184
Chang LS, Shi Y, 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
Chatterjee S, Johnson PR, Wong KK (1992) Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector. Science 258: 1485–1488
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
Cheung AK, Hoggan MD, Hauswirth WW, Berns KI (1980) Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. J Virol 33: 739–748
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.
Das HK, Jackson CL, Miller DA, Leff T, Breslow JL (1987) The human apolipoprotein C-II gene sequence contains a novel chromosome 19-specific minisatellite in its third intron. J Biol Chem 262: 4787–4793
Dixit M, Webb MS, Smart WC, Ohi S (1991) Construction and expression of a recombinant adeno-associated virus that harbors a human beta-globin-encoding cDNA. Gene 104: 253–257
Flotte TR (1993) Prospects for virus-based gene therapy for cystic fibrosis. J Bioenerg Biomembr 25: 37–42
Flotte TR, Solow R, Owens RA, Afione S, Zeitlin PL, Carter BJ (1992) Gene expression from adeno-associated virus vectors in airway epithelial cells. Am J Respir Cell Mol Biol 7: 349–356
Flotte TR, Afione SA, Solow R, Drumm ML, Markakis D, Guggino WB, Zeitlin PL, Carter BJ (1993a) Expression of the cystic fibrosis transmembrane conductance regulator from a novel adenoassociated virus promoter. J Biol Chem 268: 3781–3790
Flotte TR, Afione SA, Conrad C, Mrath SA, Solow R, Oka H, Zeitlin PL, Guggino WB, Carter BJ (1993b) Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc Natl Acad Sci USA 90: 10613–10617
Giraud C, Winocour E, Berns KI (1994) Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence. Proc Natl Acad Sci USA 91: 10039–10043
Giraud C, Winocour E, Berns KI (1995) Recombinant junctions formed by site-specific integration of adeno-associated virus into an episome. J Virol 69: 6917–6924
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
Handa H, Shiroki K, Shimojo H (1977) Establishment and characterization of KB cells lines latently infected with adeno-associated virus type 1. Virology 82: 84–92
Hauswirth WW, Berns KI (1979) Adeno-associated virus DNA replication: non unit-length molecules. Virology 93: 57–68
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
Hermonat PL, Labow MA, Wright R, Berns KI, Muzyczka N (1984) Genetics of adeno-associated virus: isolation and preliminary characterization of adeno-associated virus type 2 mutants. J Virol 51: 329–339
Hoggan MD, Blacklow NR, Rowe WP (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc Natl Acad Sci USA 55: 1457–1471
Hoggan MD, Thomas GF, Thomas FB, Johnson FB (1972) Continuous “carriage” of adenovirus associated genome in cell cultures in the absence of helper adenoviruses. Proceedings of the 4th Lepetit Colloquium. Cocoyac, Mexico. North Holland Publishing Co., Amsterdam
Hong G, Ward P, Berns KI (1994) Intermediates of adeno-associated virus DNA replication in vitro. J Virol 68: 2011–2015
Im DS, Muzyczka N (1989) Factors that bind to adeno-associated virus terminal repeats. J Virol 63: 3095–3104
Im DS, Muzyczka N (1990) The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell 61: 447–457
Im DS, Muzyczka N (1992) Partial purification of adeno-associated virus Rep78, Rep52, and Rep40 and their biochemical characterization. J Virol 66: 1119–1128
Janik JE, Huston MM, Cho K, Rose JA (1989) Efficient synthesis of adeno-associated virus structural proteins requires both adenovirus DNA binding protein and VA I RNA. Virology 168: 320–329
Jay FT, de la Maza LM, Carter BJ (1979) Parvovirus RNA transcripts containing sequences not present in mature mRNA: a method for isolation of putative NA precursor sequences. Proc Natl Acad Sci USA 76: 625–629
Kaplitt MG, Leone P, Samulski RJ, Xiao X, Pfaff DW, O’Malley KL, During MJ (1994) Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nature Genet 8: 148–154
Klein-Bauernschmitt P, zur Hausen H, Schlehofer JR (1992) Induction of differentiation-associated changes in established human cells by infection with adeno-associated virus type 2. J Virol 66: 4191–4200
Kotin RM (1994) Prospects for the use of adeno-associated virus as a vector for human gene therapy. Hum Gene Ther 5: 793–801
Kotin RM, Berns KI (1989) Organization of adeno-associated virus DNA in latently infected Detroit 6 cells. Virology 170: 460–467
Kotin RM, Siniscalco M, Samulski RJ, Zhu XD, Hunter L, Laughlin CA, Maughlin S, Muzyczka N, Rocchi M, Berns KI (1990) Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 87: 2211–2215
Kotin RM, Menninger JC, Ward DC, Berns KI (1991) Mapping and direct visualization of a regionspecific viral DNA integration site on chromosome 19q13-qter. Genomics 10: 831–834
Kotin RM, Linden RM, Berns KI (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
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. J Virol 62: 1705–1712
Labow MA, Hermonat PL, Berns KI (1986) Positive and negative autoregulation of the adeno-associated virus type 2 genome. J Virol 60: 251–258
LaFace D, Hermonat P, Wakeland E, Peck A (1988) Gene transfer into hematopoietic progenitor cells mediated by an adeno-associated virus vector. Virology 162: 483–486
Laughlin CA, Tratschin JD, Coon H, Carter BJ (1983) Cloning of infectious adeno-associated virus genomes in bacterial plasmids. Gene 23: 65–73
Laughlin CA, Cardellichio CB, Coon HC (1986) Latent infection of KB cells with adeno-associated virus type 2. J Virol 60: 515–524
Lebkowski JS, Mally MM, Okarma TB, Lerch LB (1988) Adeno-associated virus: a vector system for efficient introduction and integration of DNA into a variety of mammalian cell types. Mol Cell Biol 8: 3988–3996
Leonard CJ, Berns KI (1994a) Cloning, expression, and partial purification of Rep78: an adeno-associated virus replication protein. Virology 200: 566–573
Leonard CJ, Berns KI (1994b) Adeno-associated virus type 2: a latent life cycle. Prog Nucleic Acid Res Mol Biol 48: 29–52
Margolskee RF (1992) Epstein-Barr virus based expression vectors. In: Muzyczka N (ed) Viral expression vectors. Springer, Berlin Heidelberg New York, pp 67–95 (Current topics in microbiology and immunology vol 158)
McCarty DM, Pereira DJ, Zolotukhin I, Zhou X, Ryan JH, Muzyczka N (1994a) Identification of linear DNA sequences that specifically bind the adeno-associated virus rep protein. J Virol 68: 4988–4997
McCarty DM, Ryan JH, Zolotukhin S, Zhou X, Muzyczka N (1994b) Interaction of the adeno-associated virus rep protein with a sequence within the A palindrome of the viral terminal repeat. J Virol 68: 4998–5006
McLaughlin SK, Collis P, Hermonat PL, Muzyczka N (1988) Adeno-associated virus general transduction vectors: analysis of proviral structures. J Virol 62: 1963–1973
Mendelson E, Trempe JP, Carter BJ (1986) Identification of the transacting Rep proteins of adeno-associated virus by antibodies to a synthetic oligopeptide. J Virol 60: 823–832
Miller JL, Walsh CE, Ney PA, Samulski RJ, Nienhuis AW (1993a) Single-copy transduction and expression of human y-globin in K562 erythroleukemia cells using recombinant adeno-associated virus vectors: the effect of mutations in NF-E2 and GATA-1 binding motifs within the hypersensitivity site 2 enhancer. Blood 82: 1900–1906
Miller JL, Walsh CE, Samulski RJ, Young NS, Nienhuis AW (1993b) Transfer and expression of human-γ-globin gene in purified hematopoeitic progenitor cells from Rhesus bone marrow using a recombinant adeno-associated viral (rAAV) vector (abstract). 5th parvovirus workshop, Cristal River, FL, USA
Miller JL, Donahue RE, Sellers SE, Samulski RJ, Young NS, Nienhuis AW (1994) Recombinant adenoassociated virus (rAAV)-mediated expression of human g-globin gene in human progenitor-derived erythroid cells. Proc Natl Acad Sci USA 91: 10183–10187
Mishra L, Rose JA (1990) Adeno-associated virus DNA replication is induced by genes that are essential for HSV-1 DNA synthesis. Virology 179: 632–639
Muralidhar S, Becerra SP, Rose JA (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
Muro-Cacho CA, Samulski RJ, Kaplan D (1992) Gene transfer in human lymphocytes using a vector based on adeno-associated virus. J Immunother 11: 231–237
Muzyczka N (1992) Use of adeno-associated virus as a general transduction vector for mammalian cells. In: Muzyczka N (ed) Viral expression vectors. Springer, Berlin Heidelberg New York, pp 97–129 (Current topics in microbiology and immunology, vol 158)
Nevins JR (1982) Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A product. Cell 29: 213–220
Ni TH, Zhou X, Marty DM, Zolotukhin I, Muzyczka N (1994) In vitro replication of adeno-associated virus DNA. J Virol 68: 1128–1138
Ohi S, Dixit M, Tillery MK, Plonk SG (1989) Construction and replication of an adeno-associated virus expression vector that contains human beta-globin cDNA. Gene 89: 279–282
Philip R, Brunette E, Kilinski L, Murugesh D, Nally MA, Ucar K, Rosenblatt J, Okarma TB, Lebkowski JS (1994) Efficient and sustained gene expression in primary T lympocytes and primary and cultured tumor cells mediated by adeno-associated virus plasmid DNA complexed to cationic liposomes. Mol Cell Biol 14: 2411–2418
Podsakoff G, Wong K Jr, Chatterjee S (1994) Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors. J Virol 68: 5656–5666
Ponnazhagan S, Nallari ML, Srivastava A (1994) Suppression of human α-globin gene expression mediated by the recombinant adeno-associated virus 2-based antisense vectors. J Exp Med 179: 733–738
Ponticelli SA, Smith GR (1992) Chromosomal context dependence of a eukariotic recombinational hot spot. Proc Natl Acad Sci USA 89: 227–231
Richardson WD, Westphal H (1981) A cascade of adenovirus early functions is required for expression of adeno-associated virus. Cell 27: 133–141
Richardson WD, Westphal HC (1984) Requirement for either early region 1a or early region 1b adenovirus gene products in the helper effect for adeno-associated virus. J Virol 51: 404–410
Richardson WD, Carter BJ, Westphal H (1980) Vero cells injected with adenovirus type 2 mRNA produce authentic viral polypeptide patterns: early mRNA promoted growth of adeno-associated virus. Proc Natl Acad Sci USA 77: 931–935
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
Samulski RJ, Berns KI, Tan M, Muzyczka N (1982) Cloning of adeno-associated virus into R322: rescue of intact virus from the recombinant plasmid in human cells. Proc Natl Acad Sci USA 79: 2077–2081
Samulski RJ (1993) Adeno-associated virus: integration at a specific chromosomal locus. Curr Opin Genet Dev 3: 74–80
Samulski RJ, Shenk T (1988) Adenovirus E1B 55-Mr polypeptide facilitates timely cytoplasmic accumulation of adeno-associated virus mRNAs. J Virol 62: 206–210
Samulski RJ, Srivastava A, Berns KI, Muzyczka N (1983) Rescue of adeno-associated virus from recombinant plasmids: gene correction within the terminal repeats of AAV. Cell 33: 135–143
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: 3096–3101
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
Samulski RJ, Zhu X, Xia X, Brook JD, Housman DE, Epstein N, Hunter LA (1991) Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J 10: 3941–3950
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 helpervirus dependent parvovirus. Virology 152: 110–117
Schuchert P, Langsford M, Kaslin E, Kohli J (1991) A specific DNA sequence is required for high frequency of recombination in the ade 6 gene of fission yeast. EMBO J 10: 2157–2163
Senapathy P, Tratschin JD, Carter BJ (1984) Replication of adeno-associated virus DNA. Complementation of naturally occurring rep-mutants by a wild-type genome or an orimutant and correction of terminal palindrome deletions. J Mol Biol 179: 1–20
Shelling AN, Smith MG (1994) Targeted integration of transfected and infected adeno-associated virus vectors containing the neomycin resistant gene. Gene Ther 1: 165–169
Siegl G, Bates RC, Berns KI, Carter BJ, Kelly DC, Kurstak E, Tattersall P (1985) Characteristics and taxonomy of parvoviridae. Intervirology 23: 61–73
Snyder RO, Im D-S, Ni T, Xiao X, Samulski RJ, Muzyczka N (1993) Features of the adeno-associated virus origin involved in substrate recognition by the viral rep protein. J Virol 67: 6096–6104
Srivastava A (1987) Replication of the adeno-associated virus DNA termini in vitro. Intervirology 27: 138–147
Srivastava A, Lusby EW, Berns KI (1983) Nucleotide sequence and organization of the adeno-associated virus 2 genome. J Virol 45: 555–564
Stillman BW, Lewis JB, Chow LT, Matthews MB, Smart JE (1981) Identification of the gene for the adenovirus terminal protein precursor. Cell 23: 497–508
Stillman BW, Tamonoi F, Matthews MB (1982) Purification of an adenovirus-coded DNA polymerase that is required for initiation of DNA replication. Cell 31: 613–623
Straus SE, Sebring E, Rose JA (1976) Concatemers of alterning plus and minus strands are intermediates in adeno-associated virus DNA synthesis. Proc Natl Acad Sci USA 73: 742–746
Tratschin JD, Miller IL, Carter BJ (1984a) 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
Tratschin JD, West MH, Sandbank T, Carter BJ (1984b) A human parvovirus, adeno-associated virus, as a eucaryotic vector: transient expression and encapsidation of the procaryotic gene for chloramphenicol acetyltransferase. Mol Cell Biol 4: 2072–2081
Tratschin JD, 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
Tratschin JD, Tal J, Carter BJ (1986) Negative and positive regulation in trans of gene expression from adeno-associated virus vectors in mammalian cells by a viral rep gene product. Mol Cell Biol 6: 2884–2894
Trempe JP, Carter BJ (1988) Alternate NA splicing is required for synthesis of adeno-associated virus VP1 capsid protein. J Virol 62: 3356–3363
Urcelay E, Ward P, Wiener SM, Safer B, Kotin RM (1995) Asymmetric replication in vitro from a human sequence element is dependent on adeno-associated virus rep protein. J Virol 69: 2038–2046
Vincent KA, Moore GK, Haigwood NL (1990) Replication and packaging of HIV envelope genes in a novel adeno-associated virus vector system. Vaccines 90: 353–359
Walsh CE, Liu JM, Xiao X, Young NS, Nienhuis AW, Samulski RJ (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
Walsh CE, Liu JM, Miller JL, Nienhuis AW, Samulski RJ (1993) Gene therapy for human hemoglobinopathies. Proc Soc Exp Biol Med 204: 289–300
Walz C, Schlehofer JR (1992) Modification of some biological properties of Ha cells containing adeno-associated virus DNA integrated into chromosome 17. J Virol 66: 2990–3002
Walz C, Schlehofer JR, Flentje M, Rudat V, zur Hausen H (1992) Adeno-associated virus sensitizes Ha cell tumors to gamma rays. J Virol 66: 5651–5657
Ward P, Urcelay E, Kotin R, Safer B, Berns KI (1994) Adeno-associated virus DNA replication in vitro: activation by a maltose binding protein/Rep 68 fusion protein. J Virol 68: 6029–6037
Wei J-F, Wei F-S, Samulski RJ, Barranger JA (1994) Expression of the human glucocerebrosidase and arylsulfatase A genes in murine and patient primary fibroblasts transduced by an adeno-associated virus vector. Gene Ther 1: 261–268
Weindler FW, Heilbronn R (1991) A subset of herpes simplex virus replication genes provides helper functions for productive adeno-associated virus replication. J Virol 65: 2476–2483
Weitzman MD, Kyostio SR, Kotin RM, Owens RA (1994) Adeno-associated 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
West MH, Trempe JP, Tratschin JD, Carter BJ (1987) Gene expression in adeno-associated virus vectors: the effects of chimeric NA structure, helper virus, and adenovirus VA1 RNA. Virology 160: 38–47
Winocour E, Callaham MF, Huberman E (1988) Perturbation of the cell cycle by adeno-associated virus. Virology 167: 393–399
Winocour E, Puzis L, Etkin S, Koch T, Danovitch B, Mendelson E, Shaulian E, Karby S, Lavi S (1992) Modulation of the cellular phenotype by integrated adeno-associated virus. Virology 190: 316–329
Wu BJ, Hurst HC, Jones NC, Morimoto RJ (1986) The E1A 13S product of adenovirus 5 activates transcription of the cellular human HSP70 gene. Mol Cell Biol 6: 2994–2999
Wu P, Ziska D, Bonell MA, Grouzmann E, Millard WJ, Meyer EM (1994) Differential neuropeptide Y gene expression in post-mitotic versus dividing neuroblastoma cells driven by an adeno-associated virus vector. Mol Brain Res 24: 27–33
Xiao X, dlaminck W, Monahan J (1993) Adeno-associated virus (AAV) vectors for gene transfer. Adv Drug Deliv Rev 12: 201–215
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
Yakobson B, Hrynko TA, Peak MJ, Winocour E (1989) Replication of adeno-associated virus in cells irradiated with UV light at 254 nm. J Virol 63: 1023–1030
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: 3123–3129
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
Zhou SZ, Broxmeyer HE, Cooper S, Harrington MA, Srivastava A (1993) Adeno-associated virus 2-mediated gene transfer in murine hematopoieteic progenitor cells. Exp Hematol 21: 928–933
Zhou SZ, Cooper S, Kang LY, Ruggieri L, Heimfeld S, Srivastava A, Broxmeyer HE (1994) Adenoassociated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood. J Exp Med 179: 1867–1875
Zhu X (1993) Characterization of adeno-associated virus proviral structure in latently infected human cells. Doctor of philosophy. Pittsburgh, 1993
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Berns, K.I., Giraud, C. (1996). Biology of Adeno-associated Virus. 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_1
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