Abstract
During the past decade, in vivo administration of viral gene transfer vectors for treatment of numerous human diseases has been brought from bench to bedside in the form of clinical trials, mostly aimed at establishing the safety of the protocol. In preclinical studies in animal models of human disease, adeno-associated viral (AAV) vectors have emerged as a favored gene transfer system for this approach. These vectors are derived from a replication-deficient, non-pathogenic parvovirus with a single-stranded DNA genome. Efficient gene transfer to numerous target cells and tissues has been described. AAV is particularly efficient in transduction of non-dividing cells, and the vector genome persists predominantly in episomal forms. Substantial correction, and in some instances complete cure, of genetic disease has been obtained in animal models of hemophilia, lysosomal storage disorders, retinal diseases, disorders of the central nervous system, and other diseases. Therapeutic expression often lasted for months to years. Treatments of genetic disorders, cancer, and other acquired diseases are summarized in this review. Vector development, results in animals, early clinical experience, as well as potential hurdles and challenges are discussed.
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References
Aartsma-Rus A, Janson AA, Kaman WE, Bremmer-Bout M, van Ommen GJ, den Dunnen JT, van Deutekom JC (2004) Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense. Am J Hum Genet 74:83–92
Abmayr S, Gregorevic P, Allen JM, Chamberlain JS (2005) Phenotypic improvement of dystrophic muscles by rAAV/microdystrophin vectors is augmented by Igf1 codelivery. Mol Ther 12:441–450
Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28:92–95
Adriaansen J, Tas SW, Klarenbeek PL, Bakker AC, Apparailly F, Firestein GS, Jorgensen C, Vervoordeldonk MJ, Tak PP (2005) Enhanced gene transfer to arthritic joints using adeno-associated virus type 5: implications for intra-articular gene therapy. Ann Rheum Dis 64:1677–1684
Afione SA, Conrad CK, Kearns WG, Chunduru S, Adams R, Reynolds TC, Guggino WB, Cutting GR, Carter BJ, Flotte TR (1996) In vivo model of adeno-associated virus vector persistence and rescue. J Virol 70:3235–3241
Ahmed BY, Chakravarthy S, Eggers R, Hermens WT, Zhang JY, Niclou SP, Levelt C, Sablitzky F, Anderson PN, Lieberman AR, Verhaagen J (2004) Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors. BMC Neurosci 5:4
Alexander IE, Russell DW, Miller AD (1994) DNA-damaging agents greatly increase the transduction of nondividing cells by adeno-associated virus vectors. J Virol 68:8282–8287
Apparailly F, Khoury M, Vervoordeldonk MJ, Adriaansen J, Gicquel E, Perez N, Riviere C, Louis-Plence P, Noel D, Danos O, Douar AM, Tak PP, Jorgensen C (2005) Adeno-associated virus pseudotype 5 vector improves gene transfer in arthritic joints. Hum Gene Ther 16:426–434
Arai Y, Kubo T, Fushiki S, Mazda O, Nakai H, Iwaki Y, Imanishi J, Hirasawa Y (2000) Gene delivery to human chondrocytes by an adeno associated virus vector. J Rheumatol 27:979–982
Arruda VR, Hagstrom JN, Deitch J, Heiman-Patterson T, Camire RM, Chu K, Fields PA, Herzog RW, Couto LB, Larson PJ, High KA (2001a) Posttranslational modifications of recombinant myotube-synthesized human factor IX. Blood 97:130–138
Arruda VR, Fields PA, Milner R, Wainwright L, De Miguel MP, Donovan PJ, Herzog RW, Nichols TC, Biegel JA, Razavi M, Dake M, Huff D, Flake AW, Couto L, Kay MA, High KA (2001b) Lack of germline transmission of vector sequences following systemic administration of recombinant AAV-2 vector in males. Mol Ther 4:586–592
Arruda VR, Schuettrumpf J, Herzog RW, Nichols TC, Robinson N, Lotfi Y, Mingozzi F, Xiao W, Couto LB, High KA (2004a) Safety and efficacy of factor IX gene transfer to skeletal muscle in murine and canine hemophilia B models by adeno-associated viral vector serotype 1. Blood 103:85–92
Arruda VR, Stedman HH, Schuettrumpf J, Jiang H, Pierce G, Nichols TC, High KA (2004b) A novel method of regional intravenous delivery of AAV vector to skeletal muscle results in correction of canine hemophilia B phenotype. Blood 104:867a–868a
Arruda VR, Stedman HH, Nichols TC, Haskins ME, Nicholson M, Herzog RW, Couto LB, High KA (2005) Regional intravascular delivery of AAV-2-F.IX to skeletal muscle achieves long-term correction of hemophilia B in a large animal model. Blood 105:3458–3464
Auricchio A, Behling KC, Maguire AM, O’Connor EM, Bennett J, Wilson JM, Tolentino MJ (2002) Inhibition of retinal neovascularization by intraocular viral-mediated delivery of anti-angiogenic agents. Mol Ther 6:490–494
Azzouz M, Hottinger A, Paterna JC, Zurn AD, Aebischer P, Bueler H (2000) Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2. Hum Mol Genet 9:803–811
Bainbridge JW, Mistry A, De Alwis M, Paleolog E, Baker A, Thrasher AJ, Ali RR (2002) Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther 9:320–326
Bainbridge JW, Jia H, Bagherzadeh A, Selwood D, Ali RR, Zachary I (2003) A peptide encoded by exon 6 of VEGF (EG3306) inhibits VEGF-induced angiogenesis in vitro and ischaemic retinal neovascularisation in vivo. Biochem Biophys Res Commun 302:793–799
Bankiewicz KS, Eberling JL, Kohutnicka M, Jagust W, Pivirotto P, Bringas J, Cunningham J, Budinger TF, Harvey-White J (2000) Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 164:2–14
Behling KC, Surace EM, Bennett J (2002) Pigment epithelium-derived factor expression in the developing mouse eye. Mol Vis 8:449–454
Beretta E, Dube MG, Kalra PS, Kalra SP (2002) Long-term suppression of weight gain, adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes. Pediatr Res 52:189–198
Bergmann KJ, Mendoza MR, Yahr MD (1987) Parkinson’s disease and long-term levodopa therapy. Adv Neurol 45:463–467
Berlinghoff S, Veldwijk MR, Laufs S, Maser HP, Jauch A, Wenz F, Jens Zeller W, Fruehauf S (2004) Susceptibility of mesothelioma cell lines to adeno-associated virus 2 vector-based suicide gene therapy. Lung Cancer 46:179–186
Blake DJ, Weir A, Newey SE, Davies KE (2002) Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 82:291–329
Bosch A, Perret E, Desmaris N, Heard JM (2000) Long-term and significant correction of brain lesions in adult mucopolysaccharidosis type VII mice using recombinant AAV vectors. Mol Ther 1:63–70
Burger C, Gorbatyuk OS, Velardo MJ, Peden CS, Williams P, Zolotukhin S, Reier PJ, Mandel RJ, Muzyczka N (2004) Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol Ther 10:302–317
Burger C, Nguyen FN, Deng J, Mandel RJ (2005) Systemic mannitol-induced hyperosmolality amplifies rAAV2-mediated striatal transduction to a greater extent than local co-infusion. Mol Ther 11:327–331
Burkhardt BR, Parker MJ, Zhang YC, Song S, Wasserfall CH, Atkinson MA (2005) Glucose transporter-2 (GLUT2) promoter mediated transgenic insulin production reduces hyperglycemia in diabetic mice. FEBS Lett 579:5759–5764
Burton M, Nakai H, Colosi P, Cunningham J, Mitchell R, Couto L (1999) Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein. Proc Natl Acad Sci USA 96:12725–12730
Buzin CH, Feng J, Yan J, Scaringe W, Liu Q, den Dunnen J, Mendell JR, Sommer SS (2005) Mutation rates in the dystrophin gene: a hotspot of mutation at a CpG dinucleotide. Hum Mutat 25:177–188
Carter JD, Chen M, Ellett JD, Smith KM, Nadler JL, Yang Z (2004) Impact of donor immune cells in pancreatic islet transplantation. Transplant Proc 36:2866–2868
Carter JD, Ellett JD, Chen M, Smith KM, Fialkow LB, McDuffie MJ, Tung KS, Nadler JL, Yang Z (2005) Viral IL-10-mediated immune regulation in pancreatic islet transplantation. Mol Ther 12:360–368
Chan JM, Villarreal G, Jin WW, Stepan T, Burstein H, Wahl SM (2002) Intraarticular gene transfer of TNFR:Fc suppresses experimental arthritis with reduced systemic distribution of the gene product. Mol Ther 6:727–736
Chao H, Liu Y, Rabinowitz J, Li C, Samulski RJ, Walsh CE (2000) Several log increase in therapeutic transgene delivery by distinct adeno-associated viral serotype vectors. Mol Ther 2:619–623
Chao H, Monahan PE, Liu Y, Samulski RJ, Walsh CE (2001) Sustained and complete phenotype correction of hemophilia B mice following intramuscular injection of AAV1 serotype vectors. Mol Ther 4:217–222
Chao H, Sun L, Bruce A, Xiao X, Walsh CE (2002) Expression of human factor VIII by splicing between dimerized AAV vectors. Mol Ther 5:716–722
Chao H, Mansfield SG, Bartel RC, Hiriyanna S, Mitchell LG, Garcia-Blanco MA, Walsh CE (2003) Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing. Nat Med 9:1015–1019
Chen M, Wang GJ, Diao Y, Xu RA, Xie HT, Li XY, Sun JG (2005a) Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo. World J Gastroenterol 11:4045–4051
Chen CL, Jensen RL, Schnepp BC, Connell MJ, Shell R, Sferra TJ, Bartlett JS, Clark KR, Johnson PR (2005b) Molecular characterization of adeno-associated viruses infecting children. J Virol 79:14781–14792
Chen J, Wu Q, Yang P, Hsu HC, Mountz JD (2006) Determination of specific CD4 and CD8 T cell epitopes after AAV2- and AAV8-hF.IX gene therapy. Mol Ther 13:260–269
Cheng SH, Smith AE (2003) Gene therapy progress and prospects: gene therapy of lysosomal storage disorders. Gene Ther 10:1275–1281
Chirmule N, Propert K, Magosin S, Qian Y, Qian R, Wilson J (1999) Immune responses to adenovirus and adeno-associated virus in humans. Gene Ther 6:1574–1583
Chu CS, Trapnell BC, Curristin SM, Cutting GR, Crystal RG (1992) Extensive posttranscriptional deletion of the coding sequences for part of nucleotide-binding fold 1 in respiratory epithelial mRNA transcripts of the cystic fibrosis transmembrane conductance regulator gene is not associated with the clinical manifestations of cystic fibrosis. J Clin Invest 90:785–790
Clark KR, Voulgaropoulou F, Fraley DM, Johnson PR (1995) Cell lines for the production of recombinant adeno-associated virus. Hum Gene Ther 6:1329–1341
Conway JE, Zolotukhin S, Muzyczka N, Hayward GS, Byrne BJ (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
Conway JE, Rhys CM, Zolotukhin I, Zolotukhin S, Muzyczka N, Hayward GS, Byrne BJ (1999) High-titer recombinant adeno-associated virus production utilizing a recombinant herpes simplex virus type I vector expressing AAV-2 Rep and Cap. Gene Ther 6:986–993
Cordier L, Gao GP, Hack AA, McNally EM, Wilson JM, Chirmule N, Sweeney HL (2001) Muscle-specific promoters may be necessary for adeno-associated virus-mediated gene transfer in the treatment of muscular dystrophies. Hum Gene Ther 12:205–215
Cottard V, Mulleman D, Bouille P, Mezzina M, Boissier MC, Bessis N (2000) Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis. Gene Ther 7:1930–1939
Cresawn KO, Fraites TJ, Wasserfall C, Atkinson M, Lewis M, Porvasnik S, Liu C, Mah C, Byrne BJ (2005) Impact of humoral immune response on distribution and efficacy of recombinant adeno-associated virus-derived acid alpha-glucosidase in a model of glycogen storage disease type II. Hum Gene Ther 16:68–80
Daly TM, Okuyama T, Vogler C, Haskins ME, Muzyczka N, Sands MS (1999) Neonatal intramuscular injection with recombinant adeno-associated virus results in prolonged beta-glucuronidase expression in situ and correction of liver pathology in mucopolysaccharidosis type VII mice. Hum Gene Ther 10:85–94
Dass B, Iravani MM, Huang C, Barsoum J, Engber TM, Galdes A, Jenner P (2005) Sonic hedgehog delivered by an adeno-associated virus protects dopaminergic neurones against 6-OHDA toxicity in the rat. J Neural Transm 112:763–778
Davidoff AM, Nathwani AC, Spurbeck WW, Ng CY, Zhou J, Vanin EF (2002) rAAV-mediated long-term liver-generated expression of an angiogenesis inhibitor can restrict renal tumor growth in mice. Cancer Res 62:3077–3083
Davidoff AM, Gray JT, Ng CY, Zhang Y, Zhou J, Spence Y, Bakar Y, Nathwani AC (2005a) Comparison of the ability of adeno-associated viral vectors pseudotyped with serotype 2, 5, and 8 capsid proteins to mediate efficient transduction of the liver in murine and nonhuman primate models. Mol Ther 11:875–888
Davidoff AM, Ng CY, Zhang Y, Streck CJ, Mabry SJ, Barton SH, Baudino T, Zhou J, Kerbel RS, Vanin EF, Nathwani AC (2005b) Careful decoy receptor titering is required to inhibit tumor angiogenesis while avoiding adversely altering VEGF bioavailability. Mol Ther 11:300–310
Davidson BL, Stein CS, Heth JA, Martins I, Kotin RM, Derksen TA, Zabner J, Ghodsi A, Chiorini JA (2000) Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system. Proc Natl Acad Sci USA 97:3428–3432
De BP, Heguy A, Hackett NR, Ferris B, Leopold PL, Lee J, Pierre L, Gao G, Wilson JM, Crystal RG (2006) High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. Mol Ther 13:67–76
Dejneka NS, Surace EM, Aleman TS, Cideciyan AV, Lyubarsky A, Savchenko A, Redmond TM, Tang W, Wei Z, Rex TS, Glover E, Maguire AM, Pugh EN Jr, Jacobson SG, Bennett J (2004) In utero gene therapy rescues vision in a murine model of congenital blindness. Mol Ther 9:182–188
De la Porte S, Morin S, Koenig J (1999) Characteristics of skeletal muscle in mdx mutant mice. Int Rev Cytol 191:99–148
Dhillon H, Kalra SP, Prima V, Zolotukhin S, Scarpace PJ, Moldawer LL, Muzyczka N, Kalra PS (2001) Central leptin gene therapy suppresses body weight gain, adiposity and serum insulin without affecting food consumption in normal rats: a long-term study. Regul Pept 99:69–77
Dickson G, Roberts ML, Wells DJ, Fabb SA (2002) Recombinant micro-genes and dystrophin viral vectors. Neuromuscul Disord 12(Suppl 1):S40–S44
Dinculescu A, Glushakova L, Min SH, Hauswirth WW (2005) Adeno-associated virus-vectored gene therapy for retinal disease. Hum Gene Ther 16:649–663
Di Pasquale G, Davidson BL, Stein CS, Martins I, Scudiero D, Monks A, Chiorini JA (2003) Identification of PDGFR as a receptor for AAV-5 transduction. Nat Med 9:1306–1312
Dobrzynski E, Herzog RW (2005) Tolerance induction by viral in vivo gene transfer. Clin Med Res 3(4):234–240
Dobrzynski E, Mingozzi F, Liu Y-L, Cao O, Wang L, Herzog RW (2004) Induction of antigen-specific CD4+ T cell anergy and deletion by in vivo viral gene transfer. Blood 104:969–977
Dobrzynski E, Fitzgerald JC, Cao O, Mingozzi F, Wang L, Herzog RW (2006) Prevention of cytotoxic T lymphocyte responses to factor IX expressing hepatocytes by gene transfer-induced regulatory T cells. Proc Natl Acad Sci USA 103(12):4592–4597
Driskell RA, Engelhardt JF (2003) Current status of gene therapy for inherited lung diseases. Annu Rev Physiol 65:585–612
Duan D, Sharma P, Yang J, Yue Y, Dudus L, Zhang Y, Fisher KJ, Engelhardt JF (1998a) Circular intermediates of recombinant adeno-associated virus have defined structural characteristics responsible for long-term episomal persistence in muscle tissue. J Virol 72:8568–8577
Duan D, Yue Y, Yan Z, McCray PB Jr, Engelhardt JF (1998b) Polarity influences the efficiency of recombinant adenoassociated virus infection in differentiated airway epithelia. Hum Gene Ther 9:2761–2776
Duan D, Yue Y, Yan Z, Engelhardt JF (2000a) A new dual-vector approach to enhance recombinant adeno-associated virus-mediated gene expression through intermolecular cis activation. Nat Med 6:595–598
Duan D, Yue Y, Yan Z, Yang J, Engelhardt JF (2000b) Endosomal processing limits gene transfer to polarized airway epithelia by adeno-associated virus. J Clin Invest 105:1573–1587
Duan D, Yue Y, Engelhardt JF (2001) Expanding AAV packaging capacity with trans-splicing or overlapping vectors: a quantitative comparison. Mol Ther 4:383–391
Dube MG, Beretta E, Dhillon H, Ueno N, Kalra PS, Kalra SP (2002) Central leptin gene therapy blocks high-fat diet-induced weight gain, hyperleptinemia, and hyperinsulinemia: increase in serum ghrelin levels. Diabetes 51:1729–1736
Dumon KR, Ishii H, Fong LY, Zanesi N, Fidanza V, Mancini R, Vecchione A, Baffa R, Trapasso F, During MJ, Huebner K, Croce CM (2001a) FHIT gene therapy prevents tumor development in Fhit-deficient mice. Proc Natl Acad Sci USA 98:3346–3351
Dumon KR, Ishii H, Vecchione A, Trapasso F, Baldassarre G, Chakrani F, Druck T, Rosato EF, Williams NN, Baffa R, During MJ, Huebner K, Croce CM (2001b) Fragile histidine triad expression delays tumor development and induces apoptosis in human pancreatic cancer. Cancer Res 61:4827–4836
During MJ, Symes CW, Lawlor PA, Lin J, Dunning J, Fitzsimons HL, Poulsen D, Leone P, Xu R, Dicker BL, Lipski J, Young D (2000) An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science 287:1453–1460
Ehrenpreis J, Hillers M, Junkes B, Pfordt M, Schwinger E, Vosberg HP (1991) Analysis of a dystrophin gene deletion by amplification of mRNA isolated from DMD myotubes cultured in vitro. Genomics 10:551–557
Elliger SS, Elliger CA, Aguilar CP, Raju NR, Watson GL (1999) Elimination of lysosomal storage in brains of MPS VII mice treated by intrathecal administration of an adeno-associated virus vector. Gene Ther 6:1175–1178
Ellinwood NM, Vite CH, Haskins ME (2004) Gene therapy for lysosomal storage diseases: the lessons and promise of animal models. J Gene Med 6:481–506
Erles K, Sebokova P, Schlehofer JR (1999) Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV). J Med Virol 59:406–411
Ervasti JM, Campbell KP (1993) A role for the dystrophin–glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol 122:809–823
Eslamboli A, Georgievska B, Ridley RM, Baker HF, Muzyczka N, Burger C, Mandel RJ, Annett L, Kirik D (2005) Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson’s disease. J Neurosci 25:769–777
Evans CH, Gouze JN, Gouze E, Robbins PD, Ghivizzani SC (2004) Osteoarthritis gene therapy. Gene Ther 11:379–389
Fabb SA, Wells DJ, Serpente P, Dickson G (2002) Adeno-associated virus vector gene transfer and sarcolemmal expression of a 144 kDa micro-dystrophin effectively restores the dystrophin-associated protein complex and inhibits myofibre degeneration in nude/mdx mice. Hum Mol Genet 11:733–741
Fang J, Qian JJ, Yi S, Harding TC, Tu GH, VanRoey M, Jooss K (2005) Stable antibody expression at therapeutic levels using the 2A peptide. Nat Biotechnol 23:584–590
Feng J, Yan J, Buzin CH, Towbin JA, Sommer SS (2002a) Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy. Mol Genet Metab 77:119–126
Feng J, Yan JY, Buzin CH, Sommer SS, Towbin JA (2002b) Comprehensive mutation scanning of the dystrophin gene in patients with nonsyndromic X-linked dilated cardiomyopathy. J Am Coll Cardiol 40:1120–1124
Ferrari FK, Samulski T, Shenk T, Samulski RJ (1996) Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors. J Virol 70:3227–3234
Fields PA, Arruda VR, Armstrong E, Chu K, Mingozzi F, Hagstrom JN, Herzog RW, High KA (2001) Risk and prevention of anti-factor IX formation in AAV-mediated gene transfer in the context of a large deletion of F9. Mol Ther 4:201–210
Fisher KJ, Jooss K, Alston J, Yang Y, Ehlen-Haecker S, High K, Pathak R, Raper SE, Wilson JM (1997) Recombinant adeno-associated virus for muscle directed gene therapy. Nat Med 3:306–312
Flotte TR (2004) Gene therapy progress and prospects: recombinant adenoassociated virus (rAAV) vectors. Gene Ther 11:805–810
Flotte TR (2005) Recent developments in recombinant AAV-mediated gene therapy for lung diseases. Curr Gene Ther 5:361–366
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
Flotte T, Agarwal A, Wang J, Song S, Fenjves ES, Inverardi L, Chesnut K, Afione S, Loiler S, Wasserfall C, Kapturczak M, Ellis T, Nick H, Atkinson M (2001) Efficient ex vivo transduction of pancreatic islet cells with recombinant adeno-associated virus vectors. Diabetes 50:515–520
Flotte TR, Zeitlin PL, Reynolds TC, Heald AE, Pedersen P, Beck S, Conrad CK, Brass-Ernst L, Humphries M, Sullivan K, Wetzel R, Taylor G, Carter BJ, Guggino WB (2003) Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical study. Hum Gene Ther 14:1079–1088
Flotte TR, Brantly ML, Spencer LT, Byrne BJ, Spencer CT, Baker DJ, Humphries M (2004) Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults. Hum Gene Ther 15:93–128
Fraites TJ Jr, Schleissing MR, Shanely RA, Walter GA, Cloutier DA, Zolotukhin I, Pauly DF, Raben N, Plotz PH, Powers SK, Kessler PD, Byrne BJ (2002) Correction of the enzymatic and functional deficits in a model of Pompe disease using adeno-associated virus vectors. Mol Ther 5:571–578
Franco LM, Sun B, Yang X, Bird A, Zhang H, Schneider A, Brown T, Young SP, Clay TM, Amalfitano A, Chen YT, Koeberl DD (2005) Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. Mol Ther 12:876–884
Frisella WA, O’Connor LH, Vogler CA, Roberts M, Walkley S, Levy B, Daly TM, Sands MS (2001) Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII. Mol Ther 3:351–358
Fu H, Muenzer J, Samulski RJ, Breese G, Sifford J, Zeng X, McCarty DM (2003) Self-complementary adeno-associated virus serotype 2 vector: global distribution and broad dispersion of AAV-mediated transgene expression in mouse brain. Mol Ther 8:911–917
Fukui T, Hayashi Y, Kagami H, Yamamoto N, Fukuhara H, Tohnai I, Ueda M, Mizuno M, Yoshida J (2001) Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector. Oral Oncol 37:211–215
Gao G-P, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM (2002) Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA 99:11854–11859
Gao G, Alvira MR, Somanathan S, Lu Y, Vandenberghe LH, Rux JJ, Calcedo R, Sanmiguel J, Abbas Z, Wilson JM (2003) Adeno-associated viruses undergo substantial evolution in primates during natural infections. Proc Natl Acad Sci USA 100:6081–6086
Gao G, Vandenberghe LH, Alvira MR, Lu Y, Calcedo R, Zhou X, Wilson JM (2004) Clades of adeno-associated viruses are widely disseminated in human tissues. J Virol 78:6381–6388
Gebski BL, Mann CJ, Fletcher S, Wilton SD (2003) Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdx mouse muscle. Hum Mol Genet 12:1801–1811
Gonin P, Arandel L, Van Wittenberghe L, Marais T, Perez N, Danos O (2005) Femoral intra-arterial injection: a tool to deliver and assess recombinant AAV constructs in rodents whole hind limb. J Gene Med 7:782–791
Goudy K, Song S, Wasserfall C, Zhang YC, Kapturczak M, Muir A, Powers M, Scott-Jorgensen M, Campbell-Thompson M, Crawford JM, Ellis TM, Flotte TR, Atkinson MA (2001) Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice. Proc Natl Acad Sci USA 98:13913–13918
Goudy KS, Burkhardt BR, Wasserfall C, Song S, Campbell-Thompson ML, Brusko T, Powers MA, Clare-Salzler MJ, Sobel ES, Ellis TM, Flotte TR, Atkinson MA (2003) Systemic overexpression of IL-10 induces CD4+CD25+ cell populations in vivo and ameliorates type 1 diabetes in nonobese diabetic mice in a dose-dependent fashion. J Immunol 171:2270–2278
Gould DJ, Favorov P (2003) Vectors for the treatment of autoimmune disease. Gene Ther 10:912–927
Goyenvalle A, Vulin A, Fougerousse F, Leturcq F, Kaplan JC, Garcia L, Danos O (2004) Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 306:1796–1799
Gregorevic P, Blankinship MJ, Allen JM, Crawford RW, Meuse L, Miller DG, Russell DW, Chamberlain JS (2004) Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med 10:828–834
Grifman M, Trepel M, Speece P, Gilbert LB, Arap W, Pasqualini R, Weitzman MD (2001) Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids. Mol Ther 3:964–975
Grimm D, Zhou S, Nakai H, Thomas CE, Storm TA, Fuess S, Matsushita T, Allen J, Surosky R, Lochrie M, Meuse L, McClelland A, Colosi P, Kay MA (2003) Preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for liver gene therapy. Blood 102:2412–2419
Haberman RP, Samulski RJ, McCown TJ (2003) Attenuation of seizures and neuronal death by adeno-associated virus vector galanin expression and secretion. Nat Med 9:1076–1080
Hacker UT, Wingenfeld L, Kofler DM, Schuhmann NK, Lutz S, Herold T, King SB, Gerner FM, Perabo L, Rabinowitz J, McCarty DM, Samulski RJ, Hallek M, Buning H (2005) Adeno-associated virus serotypes 1 to 5 mediated tumor cell directed gene transfer and improvement of transduction efficiency. J Gene Med 7:1429–1438
Hadaczek P, Mirek H, Bringas J, Cunningham J, Bankiewicz K (2004) Basic fibroblast growth factor enhances transduction, distribution, and axonal transport of adeno-associated virus type 2 vector in rat brain. Hum Gene Ther 15:469–479
Halbert CL, Allen JM, Miller AD (2001) Adeno-associated virus type 6 (AAV6) vectors mediate efficient transduction of airway epithelial cells in mouse lungs compared to that of AAV2 vectors. J Virol 75:6615–6624
Halbert CL, Allen JM, Miller AD (2002) Efficient mouse airway transduction following recombination between AAV vectors carrying parts of a larger gene. Nat Biotechnol 20:697–701
Hamilton JF, Morrison PF, Chen MY, Harvey-White J, Pernaute RS, Phillips H, Oldfield E, Bankiewicz KS (2001) Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. Exp Neurol 168:155–161
Han G, Li Y, Wang J, Wang R, Chen G, Song L, Xu R, Yu M, Wu X, Qian J, Shen B (2005) Active tolerance induction and prevention of autoimmune diabetes by immunogene therapy using recombinant adenoassociated virus expressing glutamic acid decarboxylase 65 peptide GAD(500–585). J Immunol 174:4516–4524
Hara H, Monsonego A, Yuasa K, Adachi K, Xiao X, Takeda S, Takahashi K, Weiner HL, Tabira T (2004) Development of a safe oral Abeta vaccine using recombinant adeno-associated virus vector for Alzheimer’s disease. J Alzheimers Dis 6:483–488
Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, Harper HA, Robinson AS, Engelhardt JF, Brooks SV, Chamberlain JS (2002) Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med 8:253–261
Harper SQ, Staber PD, He X, Eliason SL, Martins IH, Mao Q, Yang L, Kotin RM, Paulson HL, Davidson BL (2005) RNA interference improves motor and neuropathological abnormalities in a Huntington’s disease mouse model. Proc Natl Acad Sci USA 102:5820–5825
Herzog RW (2005) Recent advances in hepatic gene transfer: more efficacy and less immunogenicity. Curr Opin Drug Discov Devel 8:199–206
Herzog RW, Dobrzynski E (2004) Immune implications of gene therapy for hemophilia. Semin Thromb Hemost 30:215–226
Herzog R, Hagstrom N, Kung S, Wilson JM, Tai S, Fisher K, High KA (1997) Stable gene transfer and expression of human FIX following intramuscular injection of recombinant AAV. Proc Natl Acad Sci USA 94:5804–5809
Herzog R, Yang E, Couto L, Hagstrom J, Elwell D, Fields P, Burton M, Bellinger D, Read M, Brinkhous K, Podsakoff G, Nichols T, Kurtzman G, High K (1999) Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector. Nat Med 5:56–63
Herzog RW, Mount JD, Arruda VR, High KA, Lothrop CD Jr, Fields PA (2001) Muscle-directed gene transfer and transient immune suppression result in sustained partial correction of canine hemophilia B caused by a null mutation. Mol Ther 4:192–200
Herzog RW, Fields PA, Arruda VR, Brubaker JO, Armstrong E, McClintock D, Bellinger DA, Couto LB, Nichols TC, High KA (2002) Influence of vector dose on factor IX-specific T and B cell responses in muscle-directed gene therapy. Hum Gene Ther 13:1281–1291
Heuer GG, Passini MA, Jiang K, Parente MK, Lee VM, Trojanowski JQ, Wolfe JH (2002) Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible. Ann Neurol 52:762–770
High KA (2004) Clinical gene transfer studies for hemophilia B. Semin Thromb Hemost 30:257–267
Hong SY, Lee MH, Kim KS, Jung HC, Roh JK, Hyung WJ, Noh SH, Choi SH (2004) Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model. World J Gastroenterol 10:1191–1197
Horger BA, Nishimura MC, Armanini MP, Wang LC, Poulsen KT, Rosenblad C, Kirik D, Moffat B, Simmons L, Johnson E Jr, Milbrandt J, Rosenthal A, Bjorklund A, Vandlen RA, Hynes MA, Phillips HS (1998) Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 18:4929–4937
Hornykiewicz O, Kish SJ (1987) Biochemical pathophysiology of Parkinson’s disease. Adv Neurol 45:19–34
Isayeva T, Ren C, Ponnazhagan S (2005) Recombinant adeno-associated virus 2-mediated antiangiogenic prevention in a mouse model of intraperitoneal ovarian cancer. Clin Cancer Res 11:1342–1347
Janouskova O, Sima P, Kunke D (2003) Combined suicide gene and immunostimulatory gene therapy using AAV-mediated gene transfer to HPV-16 transformed mouse cell: decrease of oncogenicity and induction of protection. Int J Oncol 22:569–577
Janson C, McPhee S, Bilaniuk L, Haselgrove J, Testaiuti M, Freese A, Wang DJ, Shera D, Hurh P, Rupin J, Saslow E, Goldfarb O, Goldberg M, Larijani G, Sharrar W, Liouterman L, Camp A, Kolodny E, Samulski J, Leone P (2002) Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Hum Gene Ther 13:1391–1412
Jennings K, Miyamae T, Traister R, Marinov A, Katakura S, Sowders D, Trapnell B, Wilson JM, Gao G, Hirsch R (2005) Proteasome inhibition enhances AAV-mediated transgene expression in human synoviocytes in vitro and in vivo. Mol Ther 11:600–607
Johnson LG, Olsen JC, Sarkadi B, Moore KL, Swanstrom R, Boucher RC (1992) Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat Genet 2:21–25
Jooss K, Yang Y, Fisher KJ, Wilson JM (1998) Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J Virol 72:4212–4223
Kaludov N, Brown KE, Walters RW, Zabner J, Chiorini JA (2001) Adeno-associated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity. J Virol 75:6884–6893
Kanazawa T, Mizukami H, Okada T, Hanazono Y, Kume A, Nishino H, Takeuchi K, Kitamura K, Ichimura K, Ozawa K (2003) Suicide gene therapy using AAV-HSVtk/ganciclovir in combination with irradiation results in regression of human head and neck cancer xenografts in nude mice. Gene Ther 10:51–58
Kanazawa T, Mizukami H, Nishino H, Okada T, Hanazono Y, Kume A, Kitamura K, Ichimura K, Ozawa K (2004) Topoisomerase inhibitors enhance the cytocidal effect of AAV-HSVtk/ganciclovir on head and neck cancer cells. Int J Oncol 25:729–735
Kashiwakura Y, Tamayose K, Iwabuchi K, Hirai Y, Shimada T, Matsumoto K, Nakamura T, Watanabe M, Oshimi K, Daida H (2005) Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection. J Virol 79:609–614
Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH (2003) Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 301:839–842
Kaspar BK, Frost LM, Christian L, Umapathi P, Gage FH (2005) Synergy of insulin-like growth factor-1 and exercise in amyotrophic lateral sclerosis. Ann Neurol 57:649–655
Kay MA, Manno CS, Ragni MV, Larson PJ, Couto LB, McClelland A, Glader B, Chew AJ, Tai SJ, Herzog RW, Arruda V, Johnson F, Scallan C, Skarsgard E, Flake AW, High KA (2000) Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet 24:257–261
Kearns WG, Afione SA, Fulmer SB, Pang MC, Erikson D, Egan M, Landrum MJ, Flotte TR, Cutting GR (1996) Recombinant adeno-associated virus (AAV-CFTR) vectors do not integrate in a site-specific fashion in an immortalized epithelial cell line. Gene Ther 3:748–755
Kells AP, Fong DM, Dragunow M, During MJ, Young D, Connor B (2004) AAV-mediated gene delivery of BDNF or GDNF is neuroprotective in a model of Huntington disease. Mol Ther 9:682–688
Kirik D, Georgievska B, Burger C, Winkler C, Muzyczka N, Mandel RJ, Bjorklund A (2002) Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of l-dopa using rAAV-mediated gene transfer. Proc Natl Acad Sci USA 99:4708–4713
Klein RL, Hirko AC, Meyers CA, Grimes JR, Muzyczka N, Meyer EM (2000) NGF gene transfer to intrinsic basal forebrain neurons increases cholinergic cell size and protects from age-related, spatial memory deficits in middle-aged rats. Brain Res 875:144–151
Klein RL, Dayton RD, Leidenheimer NJ, Jansen K, Golde TE, Zweig RM (2006) Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins. Mol Ther 13(3):517–527
Klugmann M, Leichtlein CB, Symes CW, Serikawa T, Young D, During MJ (2005a) Restoration of aspartoacylase activity in CNS neurons does not ameliorate motor deficits and demyelination in a model of Canavan disease. Mol Ther 11:745–753
Klugmann M, Wymond Symes C, Leichtlein CB, Klaussner BK, Dunning J, Fong D, Young D, During MJ (2005b) AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats. Mol Cell Neurosci 28:347–360
Koenig M, Kunkel LM (1990) Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer flexibility. J Biol Chem 265:4560–4566
Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53:219–226
Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T, Meng G, Muller CR, Lindlof M, Kaariainen H et al (1989) The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 45:498–506
Kok MR, Baum BJ, Tak PP, Pillemer SR (2003a) Use of localised gene transfer to develop new treatment strategies for the salivary component of Sjogren’s syndrome. Ann Rheum Dis 62:1038–1046
Kok MR, Yamano S, Lodde BM, Wang J, Couwenhoven RI, Yakar S, Voutetakis A, Leroith D, Schmidt M, Afione S, Pillemer SR, Tsutsui MT, Tak PP, Chiorini JA, Baum BJ (2003b) Local adeno-associated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of Sjogren’s syndrome. Hum Gene Ther 14:1605–1618
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
Kunke D, Grimm D, Denger S, Kreuzer J, Delius H, Komitowski D, Kleinschmidt JA (2000) Preclinical study on gene therapy of cervical carcinoma using adeno-associated virus vectors. Cancer Gene Ther 7:766–777
Lai Y, Yue Y, Liu M, Ghosh A, Engelhardt JF, Chamberlain JS, Duan D (2005a) Efficient in vivo gene expression by trans-splicing adeno-associated viral vectors. Nat Biotechnol 23:1435–1439
Lai CC, Wu WC, Chen SL, Sun MH, Xiao X, Ma L, Lin KK, Tsao YP (2005b) Recombinant adeno-associated virus vector expressing angiostatin inhibits preretinal neovascularization in adult rats. Ophthalmic Res 37:50–56
Lalani AS, Chang B, Lin J, Case SS, Luan B, Wu-Prior WW, VanRoey M, Jooss K (2004) Anti-tumor efficacy of human angiostatin using liver-mediated adeno-associated virus gene therapy. Mol Ther 9:56–66
Landgraf R, Frank E, Aldag JM, Neumann ID, Sharer CA, Ren X, Terwilliger EF, Niwa M, Wigger A, Young LJ (2003) Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour. Eur J Neurosci 18:403–411
LaVail MM, Yasumura D, Matthes MT, Drenser KA, Flannery JG, Lewin AS, Hauswirth WW (2000) Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy. Proc Natl Acad Sci USA 97:11488–11493
Leff SE, Spratt SK, Snyder RO, Mandel RJ (1999) Long-term restoration of striatal L-aromatic amino acid decarboxylase activity using recombinant adeno-associated viral vector gene transfer in a rodent model of Parkinson’s disease. Neuroscience 92:185–196
Lewin AS, Drenser KA, Hauswirth WW, Nishikawa S, Yasumura D, Flannery JG, LaVail MM (1998) Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa. Nat Med 4:967–971
Li G, Mobbs CV, Scarpace PJ (2003) Central pro-opiomelanocortin gene delivery results in hypophagia, reduced visceral adiposity, and improved insulin sensitivity in genetically obese Zucker rats. Diabetes 52:1951–1957
Li G, Zhang Y, Wilsey JT, Scarpace PJ (2005) Hypothalamic pro-opiomelanocortin gene delivery ameliorates obesity and glucose intolerance in aged rats. Diabetologia 48:2376–2385
Lin EJ, Richichi C, Young D, Baer K, Vezzani A, During MJ (2003) Recombinant AAV-mediated expression of galanin in rat hippocampus suppresses seizure development. Eur J Neurosci 18:2087–2092
Linden RM, Ward P, Giraud C, Winocour E, Berns KI (1996a) Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 93:11288–11294
Linden RM, Winocour E, Berns KI (1996b) The recombination signals for adeno-associated virus site-specific integration. Proc Natl Acad Sci USA 93:7966–7972
Liu DW, Tsao YP, Kung JT, Ding YA, Sytwu HK, Xiao X, Chen SL (2000) Recombinant adeno-associated virus expressing human papillomavirus type 16 E7 peptide DNA fused with heat shock protein DNA as a potential vaccine for cervical cancer. J Virol 74:2888–2894
Liu YL, Wagner K, Robinson N, Sabatino D, Margaritis P, Xiao W, Herzog RW (2003) Optimized production of high-titer recombinant adeno-associated virus in roller bottles. Biotechniques 34:184–189
Liu G, Martins IH, Chiorini JA, Davidson BL (2005a) Adeno-associated virus type 4 (AAV4) targets ependyma and astrocytes in the subventricular zone and RMS. Gene Ther 12:1503–1508
Liu H, Peng CH, Liu YB, Wu YL, Zhao ZM, Wang Y, Han BS (2005b) Inhibitory effect of adeno-associated virus-mediated gene transfer of human endostatin on hepatocellular carcinoma. World J Gastroenterol 11:3331–3334
Liu M, Yue Y, Harper SQ, Grange RW, Chamberlain JS, Duan D (2005c) Adeno-associated virus-mediated microdystrophin expression protects young mdx muscle from contraction-induced injury. Mol Ther 11:245–256
Lodde BM, Mineshiba F, Wang J, Cotrim AP, Afione S, Tak PP, Baum BJ (2006) Effect of human vasoactive intestinal peptide gene transfer in a murine model of Sjogren’s syndrome. Ann Rheum Dis 65(2):195–200
Lotery AJ, Yang GS, Mullins RF, Russell SR, Schmidt M, Stone EM, Lindbloom JD, Chiorini JA, Kotin RM, Davidson BL (2003) Adeno-associated virus type 5: transduction efficiency and cell-type specificity in the primate retina. Hum Gene Ther 14:1663–1671
Lu QL, Mann CJ, Lou F, Bou-Gharios G, Morris GE, Xue SA, Fletcher S, Partridge TA, Wilton SD (2003a) Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat Med 9:1009–1014
Lu YY, Wang LJ, Muramatsu S, Ikeguchi K, Fujimoto K, Okada T, Mizukami H, Matsushita T, Hanazono Y, Kume A, Nagatsu T, Ozawa K, Nakano I (2003b) Intramuscular injection of AAV-GDNF results in sustained expression of transgenic GDNF, and its delivery to spinal motoneurons by retrograde transport. Neurosci Res 45:33–40
Lu QL, Rabinowitz A, Chen YC, Yokota T, Yin H, Alter J, Jadoon A, Bou-Gharios G, Partridge T (2005) Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc Natl Acad Sci USA 102:198–203
Lundberg C, Jungles SJ, Mulligan RC (2001) Direct delivery of leptin to the hypothalamus using recombinant adeno-associated virus vectors results in increased therapeutic efficacy. Nat Biotechnol 19:169–172
Lynch GS, Rafael JA, Chamberlain JS, Faulkner JA (2000) Contraction-induced injury to single permeabilized muscle fibers from mdx, transgenic mdx, and control mice. Am J Physiol Cell Physiol 279:C1290–C1294
Ma HI, Guo P, Li J, Lin SZ, Chiang YH, Xiao X, Cheng SY (2002a) Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin. Cancer Res 62:756–763
Ma HI, Lin SZ, Chiang YH, Li J, Chen SL, Tsao YP, Xiao X (2002b) Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector. Gene Ther 9:2–11
Ma H, Liu Y, Liu S, Kung HF, Sun X, Zheng D, Xu R (2005a) Recombinant adeno-associated virus-mediated TRAIL gene therapy suppresses liver metastatic tumors. Int J Cancer 116:314–321
Ma H, Liu Y, Liu S, Xu R, Zheng D (2005b) Oral adeno-associated virus-sTRAIL gene therapy suppresses human hepatocellular carcinoma growth in mice. Hepatology 42:1355–1363
Madry H, Cucchiarini M, Terwilliger EF, Trippel SB (2003) Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. Hum Gene Ther 14:393–402
Mah C, Qing K, Khuntirat B, Ponnazhagan S, Wang XS, Kube DM, Yoder MC, Srivastava A (1998) Adeno-associated virus type 2-mediated gene transfer: role of epidermal growth factor receptor protein tyrosine kinase in transgene expression. J Virol 72:9835–9843
Mah C, Sarkar R, Zolotukhin I, Schleissing M, Xiao X, Kazazian HH, Byrne BJ (2003) Dual vectors expressing murine factor VIII result in sustained correction of hemophilia A mice. Hum Gene Ther 14:143–152
Mah C, Cresawn KO, Fraites TJ Jr, Pacak CA, Lewis MA, Zolotukhin I, Byrne BJ (2005) Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. Gene Ther 12:1405–1409
Mandel RJ, Spratt SK, Snyder RO, Leff SE (1997) Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson’s disease in rats. Proc Natl Acad Sci USA 94:14083–4088
Mandel RJ, Rendahl KG, Spratt SK, Snyder RO, Cohen LK, Leff SE (1998) Characterization of intrastriatal recombinant adeno-associated virus-mediated gene transfer of human tyrosine hydroxylase and human GTP-cyclohydrolase I in a rat model of Parkinson’s disease. J Neurosci 18:4271–4284
Mandel RJ, Snyder RO, Leff SE (1999a) Recombinant adeno-associated viral vector-mediated glial cell line-derived neurotrophic factor gene transfer protects nigral dopamine neurons after onset of progressive degeneration in a rat model of Parkinson’s disease. Exp Neurol 160:205–214
Mandel RJ, Gage FH, Clevenger DG, Spratt SK, Snyder RO, Leff SE (1999b) Nerve growth factor expressed in the medial septum following in vivo gene delivery using a recombinant adeno-associated viral vector protects cholinergic neurons from fimbria-fornix lesion-induced degeneration. Exp Neurol 155:59–64
Manno CS, Chew AJ, Hutchison S, Larson PJ, Herzog RW, Arruda VR, Tai SJ, Ragni MV, Thompson A, Ozelo M, Couto LB, Leonard DGB, Johnson FA, McClelland A, Scallan C, Skarsgard E, Flake AW, Kay MA, High KA, Glader B (2003) AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 101:2963–2972
Manno CS, Pierce GF, Glader B, Arruda VR, Ragni MV, Rasko J, Ozelo M, Hoots K, Blatt P, Konkle B, Dake M, Kaye R, Razevi M, Zajko A, Zhender J, Nakai H, Chew AJ, Leonard DG, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, XCouto L, Ertl HCJ, High KA, Kay MA (2006) Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med (in press)
Mastakov MY, Baer K, Xu R, Fitzsimons H, During MJ (2001) Combined injection of rAAV with mannitol enhances gene expression in the rat brain. Mol Ther 3:225–232
Mastakov MY, Baer K, Kotin RM, During MJ (2002a) Recombinant adeno-associated virus serotypes 2- and 5-mediated gene transfer in the mammalian brain: quantitative analysis of heparin co-infusion. Mol Ther 5:371–380
Mastakov MY, Baer K, Symes CW, Leichtlein CB, Kotin RM, During MJ (2002b) Immunological aspects of recombinant adeno-associated virus delivery to the mammalian brain. J Virol 76:8446–8454
Matalon R, Surendran S, Rady PL, Quast MJ, Campbell GA, Matalon KM, Tyring SK, Wei J, Peden CS, Ezell EL, Muzyczka N, Mandel RJ (2003) Adeno-associated virus-mediated aspartoacylase gene transfer to the brain of knockout mouse for canavan disease. Mol Ther 7:580–587
Matsuo M (2002) Duchenne and Becker muscular dystrophy: from gene diagnosis to molecular therapy. IUBMB Life 53:147–152
McBride JL, During MJ, Wuu J, Chen EY, Leurgans SE, Kordower JH (2003) Structural and functional neuroprotection in a rat model of Huntington’s disease by viral gene transfer of GDNF. Exp Neurol 181:213–223
McCarty DM, Monahan PE, Samulski RJ (2001) Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther 8:1248–1254
McCarty DM, Fu H, Monahan PE, Toulson CE, Naik P, Samulski RJ (2003) Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther 10:2112–2118
McPhee SW, Francis J, Janson CG, Serikawa T, Hyland K, Ong EO, Raghavan SS, Freese A, Leone P (2005) Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease. Brain Res Mol Brain Res 135:112–121
Mendell JR, Buzin CH, Feng J, Yan J, Serrano C, Sangani DS, Wall C, Prior TW, Sommer SS (2001) Diagnosis of Duchenne dystrophy by enhanced detection of small mutations. Neurology 57:645–650
Miller TM, Kaspar BK, Kops GJ, Yamanaka K, Christian LJ, Gage FH, Cleveland DW (2005) Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis. Ann Neurol 57:773–776
Min SH, Molday LL, Seeliger MW, Dinculescu A, Timmers AM, Janssen A, Tonagel F, Tanimoto N, Weber BH, Molday RS, Hauswirth WW (2005) Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis. Mol Ther 12:644–651
Mingozzi F, Liu Y-L, Dobrzynski E, Kaufhold A, Liu JH, Wang Yq, Arruda VR, High KA, Herzog RW (2003) Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer. J Clin Invest 111:1347–1356
Mizuno M, Yoshida J, Colosi P, Kurtzman G (1998) Adeno-associated virus vector containing the herpes simplex virus thymidine kinase gene causes complete regression of intracerebrally implanted human gliomas in mice, in conjunction with ganciclovir administration. Jpn J Cancer Res 89:76–80
Mochizuki H, Mizuno Y (2003) Gene therapy for Parkinson’s disease. J Neural Transm Suppl 205–213
Mohr A, Henderson G, Dudus L, Herr I, Kuerschner T, Debatin KM, Weiher H, Fisher KJ, Zwacka RM (2004) AAV-encoded expression of TRAIL in experimental human colorectal cancer leads to tumor regression. Gene Ther 11:534–543
Mori K, Gehlbach P, Yamamoto S, Duh E, Zack DJ, Li Q, Berns KI, Raisler BJ, Hauswirth WW, Campochiaro PA (2002) AAV-mediated gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 43:1994–2000
Moss RB, Rodman D, Spencer LT, Aitken ML, Zeitlin PL, Waltz D, Milla C, Brody AS, Clancy JP, Ramsey B, Hamblett N, Heald AE (2004) Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 125:509–521
Mount JD, Herzog RW, Tillson DM, Goodman SA, Robinson N, McCleland ML, Bellinger D, Nichols TC, Arruda VR, Lothrop CD, High KA (2002) Sustained phenotype correction of hemophilia B dogs with a factor IX null mutation by liver-directed gene therapy. Blood 99:2670–2676
Muramatsu S, Fujimoto K, Ikeguchi K, Shizuma N, Kawasaki K, Ono F, Shen Y, Wang L, Mizukami H, Kume A, Matsumura M, Nagatsu I, Urano F, Ichinose H, Nagatsu T, Terao K, Nakano I, Ozawa K (2002) Behavioral recovery in a primate model of Parkinson’s disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes. Hum Gene Ther 13:345–354
Murphy JE, Zhou S, Giese K, Williams LT, Escobedo JA, Dwarki VJ (1997) Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin. Proc Natl Acad Sci USA 94:13921–13926
Nakai H, Iwaki Y, Kay MA, Couto LB (1999) Isolation of recombinant adeno-associated virus vector-cellular DNA junctions from mouse liver. J Virol 73:5438–5447
Nakai H, Storm TA, Kay MA (2000a) Recruitment of single-stranded recombinant adeno-associated virus vector genomes and intermolecular recombination are responsible for stable transduction of liver in vivo. J Virol 74:9451–9463
Nakai H, Storm TA, Kay MA (2000b) Increasing the size of rAAV-mediated expression cassettes in vivo by intermolecular joining of two complementary vectors. Nat Biotechnol 18:527–532
Nakai H, Yant SR, Storm TA, Fuess S, Meuse L, Kay MA (2001) Extrachromosomal recombinant adeno-associated virus vector genomes are primarly responsible for stable liver transduction in vivo. J Virol 75:6969–6975
Nakai H, Fuess S, Storm TA, Meuse LA, Kay MA (2003a) Free DNA ends are essential for concatemerization of synthetic double-stranded adeno-associated virus vector genomes transfected into mouse hepatocytes in vivo. Mol Ther 7:112–121
Nakai H, Montini E, Fuess S, Storm TA, Grompe M, Kay MA (2003b) AAV serotype 2 vectors preferentially integrate into active genes in mice. Nat Genet 34:297–302
Nakai H, Fuess S, Storm TA, Muramatsu S, Nara Y, Kay MA (2005a) Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in mice. J Virol 79:214–224
Nakai H, Wu X, Fuess S, Storm TA, Munroe D, Montini E, Burgess SM, Grompe M, Kay MA (2005b) Large-scale molecular characterization of adeno-associated virus vector integration in mouse liver. J Virol 79:3606–3614
Narfstrom K, Bragadottir R, Redmond TM, Rakoczy PE, van Veen T, Bruun A (2003a) Functional and structural evaluation after AAV.RPE65 gene transfer in the canine model of Leber’s congenital amaurosis. Adv Exp Med Biol 533:423–430
Narfstrom K, Katz ML, Ford M, Redmond TM, Rakoczy E, Bragadottir R (2003b) In vivo gene therapy in young and adult RPE65-/- dogs produces long-term visual improvement. J Hered 94:31–37
Nathwani AC, Davidoff A, Hanawa H, Zhou J, Vanin EF, Nienhuis AW (2001) Factors influencing in vivo transduction by recombinant adeno-associated viral vectors expressing the human factor IX cDNA. Blood 97:1258–1265
Nathwani AC, Davidoff AM, Hanawa H, Hu Y, Hoffer A, Nikanorov A, Slaughter C, Ng CYC, Zhou J, Lozier JN, Mandrell TD, Vanin EF, Nienhuis AW (2002) Sustained high level expresion of human factor IX (hFIX) after liver-targeted delivery of recombinant adeno-associated virus encoding the hFIX gene in rhesus macaques. Blood 100:1662–1669
Nicklin SA, Buening H, Dishart KL, de Alwis M, Girod A, Hacker U, Thrasher AJ, Ali RR, Hallek M, Baker AH (2001) Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells. Mol Ther 4:174–181
Nicklin SA, Dishart KL, Buening H, Reynolds PN, Hallek M, Nemerow GR, Von Seggern DJ, Baker AH (2003) Transductional and transcriptional targeting of cancer cells using genetically engineered viral vectors. Cancer Lett 201:165–173
Noro T, Miyake K, Suzuki-Miyake N, Igarashi T, Uchida E, Misawa T, Yamazaki Y, Shimada T (2004) Adeno-associated viral vector-mediated expression of endostatin inhibits tumor growth and metastasis in an orthotropic pancreatic cancer model in hamsters. Cancer Res 64:7486–7490
Okada H, Miyamura K, Itoh T, Hagiwara M, Wakabayashi T, Mizuno M, Colosi P, Kurtzman G, Yoshida J (1996) Gene therapy against an experimental glioma using adeno-associated virus vectors. Gene Ther 3:957–964
Okada T, Uchibori R, Iwata-Okada M, Takahashi M, Nomoto T, Nonaka-Sarukawa M, Ito T, Liu Y, Mizukami H, Kume A, Kobayashi E, Ozawa K (2005) A histone deacetylase inhibitor enhances recombinant adeno-associated virus-mediated gene expression in tumor cells. Mol Ther (in press)
Ozawa K, Fan DS, Shen Y, Muramatsu S, Fujimoto K, Ikeguchi K, Ogawa M, Urabe M, Kume A, Nakano I (2000) Gene therapy of Parkinson’s disease using adeno-associated virus (AAV) vectors. J Neural Transm Suppl 181–191
Pan RY, Xiao X, Chen SL, Li J, Lin LC, Wang HJ, Tsao YP (1999) Disease-inducible transgene expression from a recombinant adeno-associated virus vector in a rat arthritis model. J Virol 73:3410–3417
Pan RY, Chen SL, Xiao X, Liu DW, Peng HJ, Tsao YP (2000) Therapy and prevention of arthritis by recombinant adeno-associated virus vector with delivery of interleukin-1 receptor antagonist. Arthritis Rheum 43:289–297
Passini MA, Wolfe JH (2001) Widespread gene delivery and structure-specific patterns of expression in the brain after intraventricular injections of neonatal mice with an adeno-associated virus vector. J Virol 75:12382–12392
Passini MA, Lee EB, Heuer GG, Wolfe JH (2002) Distribution of a lysosomal enzyme in the adult brain by axonal transport and by cells of the rostral migratory stream. J Neurosci 22:6437–6446
Passini MA, Watson DJ, Vite CH, Landsburg DJ, Feigenbaum AL, Wolfe JH (2003) Intraventricular brain injection of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mice. J Virol 77:7034–7040
Paterna JC, Feldon J, Bueler H (2004) Transduction profiles of recombinant adeno-associated virus vectors derived from serotypes 2 and 5 in the nigrostriatal system of rats. J Virol 78:6808–6817
Peden CS, Burger C, Muzyczka N, Mandel RJ (2004) Circulating anti-wild-type adeno-associated virus type 2 (AAV2) antibodies inhibit recombinant AAV2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer in the brain. J Virol 78:6344–6359
Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA 90:3710–3714
Philpott NJ, Gomos J, Berns KI, Falck-Pedersen E (2002) A p5 integration efficiency element mediates Rep-dependent integration into AAVS1 at chromosome 19. Proc Natl Acad Sci USA 99:12381–12385
Ponder KP, Melniczek JR, Xu L, Weil MA, O’Malley TM, O’Donnell PA, Knox VW, Aguirre GD, Mazrier H, Ellinwood NM, Sleeper M, Maguire AM, Volk SW, Mango RL, Zweigle J, Wolfe JH, Haskins ME (2002) Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs. Proc Natl Acad Sci USA 99:13102–13107
Ponnazhagan S, Mahendra G, Kumar S, Shaw DR, Stockard CR, Grizzle WE, Meleth S (2004a) Adeno-associated virus 2-mediated antiangiogenic cancer gene therapy: long-term efficacy of a vector encoding angiostatin and endostatin over vectors encoding a single factor. Cancer Res 64:1781–1787
Ponnazhagan S, Mahendra G, Lima J, Aldrich WA, Jenkins CB, Ren C, Kumar S, Kallman L, Strong TV, Shaw DR, Triozzi PL (2004b) Augmentation of antitumor activity of a recombinant adeno-associated virus carcinoembryonic antigen vaccine with plasmid adjuvant. Hum Gene Ther 15:856–864
Prima V, Tennant M, Gorbatyuk OS, Muzyczka N, Scarpace PJ, Zolotukhin S (2004) Differential modulation of energy balance by leptin, ciliary neurotrophic factor, and leukemia inhibitory factor gene delivery: microarray deoxyribonucleic acid-chip analysis of gene expression. Endocrinology 145:2035–2045
Qazilbash MH, Xiao X, Seth P, Cowan KH, Walsh CE (1997) Cancer gene therapy using a novel adeno-associated virus vector expressing human wild-type p53. Gene Ther 4:675–682
Qiao C, Li J, Zhu T, Draviam R, Watkins S, Ye X, Chen C, Li J, Xiao X (2005) Amelioration of laminin-alpha2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin. Proc Natl Acad Sci USA 102:11999–12004
Qing K, Wang XS, Kube DM, Ponnazhagan S, Bajpai A, Srivastava A (1997) Role of tyrosine phosphorylation of a cellular protein in adeno-associated virus 2-mediated transgene expression. Proc Natl Acad Sci USA 94:10879–10884
Qing K, Khuntirat B, Mah C, Kube DM, Wang XS, Ponnazhagan S, Zhou S, Dwarki VJ, Yoder MC, Srivastava A (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
Qing K, Mah C, Hansen J, Zhou S, Dwarki V, Srivastava A (1999) Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Nat Med 5:71–77
Qing K, Hansen J, Weigel-Kelley KA, Tan M, Zhou S, Srivastava A (2001) Adeno-associated virus type 2-mediated gene transfer: role of cellular FKBP52 protein in transgene expression. J Virol 75:8968–8976
Rabinowitz JE, Rolling F, Li C, Conrath H, Xiao W, Xiao X, Samulski RJ (2002) Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity. J Virol 76:791–801
Raisler BJ, Berns KI, Grant MB, Beliaev D, Hauswirth WW (2002) Adeno-associated virus type-2 expression of pigmented epithelium-derived factor or Kringles 1-3 of angiostatin reduce retinal neovascularization. Proc Natl Acad Sci USA 99:8909–8914
Ravikumar B, Duden R, Rubinsztein DC (2002) Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet 11:1107–1117
Richichi C, Lin EJ, Stefanin D, Colella D, Ravizza T, Grignaschi G, Veglianese P, Sperk G, During MJ, Vezzani A (2004) Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus. J Neurosci 24:3051–3059
Rodriguez-Lebron E, Denovan-Wright EM, Nash K, Lewin AS, Mandel RJ (2005) Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington’s disease transgenic mice. Mol Ther 12:618–633
Rosenblad C, Kirik D, Devaux B, Moffat B, Phillips HS, Bjorklund A (1999) Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson’s disease after administration into the striatum or the lateral ventricle. Eur J Neurosci 11:1554–1566
Russell DW, Alexander IE, Miller AD (1995) DNA synthesis and topoisomerase inhibitors increase transduction by adeno-associated virus vectors. Proc Natl Acad Sci USA 92:5719–5723
Rutledge EA, Halbert CL, Russell DW (1998) Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. J Virol 72:309–319
Sabatino DE, Armstrong E, Edmonson S, Liu YL, Pleimes M, Schuettrumpf J, Fitzgerald J, Herzog RW, Arruda VR, High KA (2004) Novel hemophilia B mouse models exhibiting a range of mutations in the factor IX gene. Blood 104:2767–2774
Sabatino DE, Mingozzi F, Hui DJ, Chen H, Colosi P, Ertl HC, High KA (2005) Identification of mouse AAV capsid-specific CD8+ T cell epitopes. Mol Ther 12:1023–1033
Sakamoto M, Yuasa K, Yoshimura M, Yokota T, Ikemoto T, Suzuki M, Dickson G, Miyagoe-Suzuki Y, Takeda S (2002) Micro-dystrophin cDNA ameliorates dystrophic phenotypes when introduced into mdx mice as a transgene. Biochem Biophys Res Commun 293:1265–1272
Samulski RJ, Berns KI, Tan M, 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
Samulski RJ, Chang LS, 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
Sanchez-Pernaute R, Harvey-White J, Cunningham J, Bankiewicz KS (2001) Functional effect of adeno-associated virus mediated gene transfer of aromatic L-amino acid decarboxylase into the striatum of 6-OHDA-lesioned rats. Mol Ther 4:324–330
Sarkar R, Xiao W, Kazazian HH (2003) A single adeno-associated virus (AAV)-murine factor VIII vector partially corrects the hemophilia A phenotype. J Thromb Haemost 1:220–226
Sarkar R, Tetreault R, Gao G, Wang L, Bell P, Chandler R, Wilson JM, Kazazian HH Jr (2004) Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype. Blood 103:1253–1260
Sarukhan A, Camugli S, Gjata B, von Boehmer H, Danos O, Jooss K (2001) Successful interference with cellular immune responses to immunogenic proteins encoded by recombinant viral vectors. J Virol 75:269–277
Scallan CD, Lillicrap D, Jiang H, Qian X, Patarroyo-White SL, Parker AE, Liu T, Vargas J, Nagy D, Powell SK, Wright JF, Turner PV, Tinlin SJ, Webster SE, McClelland A, Couto LB (2003a) Sustained phenotypic correction of canine hemophilia A using an adeno-associated viral vector. Blood 102:2031–2037
Scallan CD, Liu T, Parker AE, Patarroyo-White SL, Chen H, Jiang H, Vargas J, Nagy D, Powell SK, Wright JF, Sarkar R, Kazazian HH, McClelland A, Couto LB (2003b) Phenotypic correction of a mouse model of hemophilia A using AAV2 vectors encoding the heavy and light chains of FVIII. Blood 102:3919–3926
Scarpace PJ, Matheny M, Tumer N (2001) Hypothalamic leptin resistance is associated with impaired leptin signal transduction in aged obese rats. Neuroscience 104:1111–1117
Scarpace PJ, Matheny M, Zhang Y, Shek EW, Prima V, Zolotukhin S, Tumer N (2002a) Leptin-induced leptin resistance reveals separate roles for the anorexic and thermogenic responses in weight maintenance. Endocrinology 143:3026–3035
Scarpace PJ, Matheny M, Zhang Y, Tumer N, Frase CD, Shek EW, Hong B, Prima V, Zolotukhin S (2002b) Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats. Neuropharmacology 42:548–561
Scarpace PJ, Matheny M, Tumer N, Cheng KY, Zhang Y (2005) Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats. Diabetologia 48:1075–1083
Scherzinger E, Sittler A, Schweiger K, Heiser V, Lurz R, Hasenbank R, Bates GP, Lehrach H, Wanker EE (1999) Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntington’s disease pathology. Proc Natl Acad Sci USA 96:4604–4609
Schnepp BC, Jensen RL, Chen CL, Johnson PR, Clark KR (2005) Characterization of adeno-associated virus genomes isolated from human tissues. J Virol 79:14793–14803
Schoensiegel F, Paschen A, Sieger S, Eskerski H, Mier W, Rothfels H, Kleinschmidt J, Schadendorf D, Haberkorn U (2004) MIA (melanoma inhibitory activity) promoter mediated tissue-specific suicide gene therapy of malignant melanoma. Cancer Gene Ther 11:408–418
Schuettrumpf J, Herzog RW, Schlachterman A, Kaufhold A, Stafford DW, Arruda VR (2005) Factor IX variants improve gene therapy efficacy for hemophilia B. Blood 105:2316–2323
Sferra TJ, Qu G, McNeely D, Rennard R, Clark KR, Lo WD, Johnson PR (2000) Recombinant adeno-associated virus-mediated correction of lysosomal storage within the central nervous system of the adult mucopolysaccharidosis type VII mouse. Hum Gene Ther 11:507–519
Sferra TJ, Backstrom K, Wang C, Rennard R, Miller M, Hu Y (2004) Widespread correction of lysosomal storage following intrahepatic injection of a recombinant adeno-associated virus in the adult MPS VII mouse. Mol Ther 10:478–491
Shek EW, Scarpace PJ (2000) Resistance to the anorexic and thermogenic effects of centrally administrated leptin in obese aged rats. Regul Pept 92:65–71
Shen Y, Muramatsu SI, Ikeguchi K, Fujimoto KI, Fan DS, Ogawa M, Mizukami H, Urabe M, Kume A, Nagatsu I, Urano F, Suzuki T, Ichinose H, Nagatsu T, Monahan J, Nakano I, Ozawa K (2000) Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson’s disease. Hum Gene Ther 11:1509–1519
Shi W, Bartlett JS (2003) RGD inclusion in VP3 provides adeno-associated virus type 2 (AAV2)-based vectors with a heparan sulfate-independent cell entry mechanism. Mol Ther 7:515–525
Shi W, Arnold GS, Bartlett JS (2001) Insertional mutagenesis of the adeno-associated virus type 2 (AAV2) capsid gene and generation of AAV2 vectors targeted to alternative cell-surface receptors. Hum Gene Ther 12:1697–1711
Shi W, Teschendorf C, Muzyczka N, Siemann DW (2002) Adeno-associated virus-mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo. Cancer Gene Ther 9:513–521
Shi W, Teschendorf C, Muzyczka N, Siemann DW (2003) Gene therapy delivery of endostatin enhances the treatment efficacy of radiation. Radiother Oncol 66:1–9
Shi J, Zheng D, Liu Y, Sham MH, Tam P, Farzaneh F, Xu R (2005) Overexpression of soluble TRAIL induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice. Cancer Res 65:1687–1692
Shklyaev S, Aslanidi G, Tennant M, Prima V, Kohlbrenner E, Kroutov V, Campbell-Thompson M, Crawford J, Shek EW, Scarpace PJ, Zolotukhin S (2003) Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats. Proc Natl Acad Sci USA 100:14217–14222
Sieger S, Jiang S, Kleinschmidt J, Eskerski H, Schonsiegel F, Altmann A, Mier W, Haberkorn U (2004) Tumor-specific gene expression using regulatory elements of the glucose transporter isoform 1 gene. Cancer Gene Ther 11:41–51
Skorupa AF, Fisher KJ, Wilson JM, Parente MK, Wolfe JH (1999) Sustained production of beta-glucuronidase from localized sites after AAV vector gene transfer results in widespread distribution of enzyme and reversal of lysosomal storage lesions in a large volume of brain in mucopolysaccharidosis VII mice. Exp Neurol 160:17–27
Snyder RO, Miao CH, Patijn GA, Spratt SK, Danos O, Nagy D, Gown AM, Winther B, Meuse L, Cohen LK, Thompson AR, Kay MA (1997) Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors. Nat Genet 16:270–276
Snyder RO, Miao C, Meuse L, Tubb J, Donahue BA, Lin H-F, Stafford DW, Patel S, Thompson AR, Nichols T, Read MS, Bellinger DA, Brinkhous KM, Kay MA (1999) Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors. Nat Med 5:64–70
Song S, Morgan M, Ellis T, Poirier A, Chesnut K, Wang J, Brantly M, Muzyczka N, Byrne BJ, Atkinson M, Flotte TR (1998) Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc Natl Acad Sci USA 95:14384–14388
Song S, Goudy K, Campbell-Thompson M, Wasserfall C, Scott-Jorgensen M, Wang J, Tang Q, Crawford JM, Ellis TM, Atkinson MA, Flotte TR (2004) Recombinant adeno-associated virus-mediated alpha-1 antitrypsin gene therapy prevents type I diabetes in NOD mice. Gene Ther 11:181–186
Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA, Petrof B, Narusawa M, Leferovich JM, Sladky JT, Kelly AM (1991) The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature 352:536–539
Streck CJ, Zhang Y, Miyamoto R, Zhou J, Ng CY, Nathwani AC, Davidoff AM (2004a) Restriction of neuroblastoma angiogenesis and growth by interferon-alpha/beta. Surgery 136:183–189
Streck CJ, Zhou J, Ng CY, Zhang Y, Nathwani AC, Davidoff AM (2004b) Longterm recombinant adeno-associated, virus-mediated, liver-generated expression of an angiogenesis inhibitor improves survival in mice with disseminated neuroblastoma. J Am Coll Surg 199:78–86
Streck CJ, Dickson PV, Ng CY, Zhou J, Hall MM, Gray JT, Nathwani AC, Davidoff AM (2006) Antitumor efficacy of AAV-mediated systemic delivery of interferon-beta. Cancer Gene Ther 13:99–106
Su H, Chang JC, Xu SM, Kan YW (1996) Selective killing of AFP-positive hepatocellular carcinoma cells by adeno-associated virus transfer of the herpes simplex virus thymidine kinase gene. Hum Gene Ther 7:463–470
Su H, Lu R, Chang JC, Kan YW (1997) Tissue-specific expression of herpes simplex virus thymidine kinase gene delivered by adeno-associated virus inhibits the growth of human hepatocellular carcinoma in athymic mice. Proc Natl Acad Sci USA 94:13891–13896
Su H, Lu R, Ding R, Kan YW (2000) Adeno-associated viral-mediated gene transfer to hepatoma: thymidine kinase/interleukin 2 is more effective in tumor killing in non-ganciclovir (GCV)-treated than in GCV-treated animals. Mol Ther 1:509–515
Su LT, Gopal K, Wang Z, Yin X, Nelson A, Kozyak BW, Burkman JM, Mitchell MA, Low DW, Bridges CR, Stedman HH (2005) Uniform scale-independent gene transfer to striated muscle after transvenular extravasation of vector. Circulation 112:1780–1788
Subramanian IV, Ghebre R, Ramakrishnan S (2005) Adeno-associated virus-mediated delivery of a mutant endostatin suppresses ovarian carcinoma growth in mice. Gene Ther 12:30–38
Summerford C, Samulski RJ (1998) Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 72:1438–1445
Sun L, Li J, Xiao X (2000) Overcoming adeno-associated virus vector size limitation through viral DNA heterodimerization. Nat Med 6:599–602
Sun JY, Krouse RS, Forman SJ, Senitzer D, Sniecinski I, Chatterjee S, Wong KK Jr (2002) Immunogenicity of a p210(BCR-ABL) fusion domain candidate DNA vaccine targeted to dendritic cells by a recombinant adeno-associated virus vector in vitro. Cancer Res 62:3175–3183
Sun B, Zhang H, Franco LM, Young SP, Schneider A, Bird A, Amalfitano A, Chen YT, Koeberl DD (2005a) Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II. Mol Ther 11:57–65
Sun B, Zhang H, Franco LM, Brown T, Bird A, Schneider A, Koeberl DD (2005b) Correction of glycogen storage disease type II by an adeno-associated virus vector containing a muscle-specific promoter. Mol Ther 11:889–898
Sun X, Krissansen GW, Fung PW, Xu S, Shi J, Man K, Fan ST, Xu R (2005c) Anti-angiogenic therapy subsequent to adeno-associated-virus-mediated immunotherapy eradicates lymphomas that disseminate to the liver. Int J Cancer 113:670–677
Takahashi H, Kato K, Miyake K, Hirai Y, Yoshino S, Shimada T (2005) Adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen-induced arthritis in mice. Clin Exp Rheumatol 23:455–461
Tarner IH, Fathman CG (2002) The potential for gene therapy in the treatment of autoimmune disease. Clin Immunol 104:204–216
Tenenbaum L, Jurysta F, Stathopoulos A, Puschban Z, Melas C, Hermens WT, Verhaagen J, Pichon B, Velu T, Levivier M (2000) Tropism of AAV-2 vectors for neurons of the globus pallidus. Neuroreport 11:2277–2283
Thomas CE, Storm TA, Huang Z, Kay MA (2004) Rapid uncoating of vector genomes is the key to efficient liver transduction with pseudotyped adeno-associated virus vectors. J Virol 78:3110–3122
Trapnell BC, Chu CS, Paakko PK, Banks TC, Yoshimura K, Ferrans VJ, Chernick MS, Crystal RG (1991) Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis. Proc Natl Acad Sci USA 88:6565–6569
Urabe M, Ding C, Kotin RM (2002) Insect cells as a factory to produce adeno-associated virus type 2 vectors. Hum Gene Ther 13:1935–1943
Veldwijk MR, Schiedlmeier B, Kleinschmidt JA, Zeller WJ, Fruehauf S (1999) Superior gene transfer into solid tumour cells than into human mobilised peripheral blood progenitor cells using helpervirus-free adeno-associated viral vector stocks. Eur J Cancer 35:1136–1142
Veldwijk MR, Fruehauf S, Schiedlmeier B, Kleinschmidt JA, Zeller WJ (2000) Differential expression of a recombinant adeno-associated virus 2 vector in human CD34+ cells and breast cancer cells. Cancer Gene Ther 7:597–604
Veldwijk MR, Berlinghoff S, Laufs S, Hengge UR, Zeller WJ, Wenz F, Fruehauf S (2004) Suicide gene therapy of sarcoma cell lines using recombinant adeno-associated virus 2 vectors. Cancer Gene Ther 11:577–584
Vezzani A (2004) Gene therapy in epilepsy. Epilepsy Curr 4:87–90
Voutetakis A, Kok MR, Zheng C, Bossis I, Wang J, Cotrim AP, Marracino N, Goldsmith CM, Chiorini JA, Loh YP, Nieman LK, Baum BJ (2004) Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics. Proc Natl Acad Sci USA 101:3053–3058
Voutetakis A, Bossis I, Kok MR, Zhang W, Wang J, Cotrim AP, Zheng C, Chiorini JA, Nieman LK, Baum BJ (2005) Salivary glands as a potential gene transfer target for gene therapeutics of some monogenetic endocrine disorders. J Endocrinol 185:363–372
Wagner JA, Moran ML, Messner AH, Daifuku R, Conrad CK, Reynolds T, Guggino WB, Moss RB, Carter BJ, Wine JJ, Flotte TR, Gardner P (1998a) A phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients with cystic fibrosis. Hum Gene Ther 9:889–909
Wagner JA, Reynolds T, Moran ML, Moss RB, Wine JJ, Flotte TR, Gardner P (1998b) Efficient and persistent gene transfer of AAV-CFTR in maxillary sinus. Lancet 351:1702–1703
Wagner JA, Messner AH, Moran ML, Daifuku R, Kouyama K, Desch JK, Manley S, Norbash AM, Conrad CK, Friborg S, Reynolds T, Guggino WB, Moss RB, Carter BJ, Wine JJ, Flotte TR, Gardner P (1999) Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Laryngoscope 109:266–274
Wagner JA, Nepomuceno IB, Messner AH, Moran ML, Batson EP, Dimiceli S, Brown BW, Desch JK, Norbash AM, Conrad CK, Guggino WB, Flotte TR, Wine JJ, Carter BJ, Reynolds TC, Moss RB, Gardner P (2002) A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. Hum Gene Ther 13:1349–1359
Walters RW, Yi SM, Keshavjee S, Brown KE, Welsh MJ, Chiorini JA, Zabner J (2001) Binding of adeno-associated virus type 5 to 2,3-linked sialic acid is required for gene transfer. J Biol Chem 276:20610–20616
Wang L, Takabe K, Bidlingmaier SM, Ill CR, Verma IM (1999) Sustained correction of bleeding disorder in hemophilia B mice by gene therapy. Proc Natl Acad Sci USA 96:3906–3910
Wang B, Li J, Xiao X (2000a) Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci USA 97:13714–13719
Wang L, Nichols TC, Read MS, Bellinger DA, Verma IM (2000b) Sustained expression of therapeutic level of factor IX in hemophilia B dogs by AAV-mediated gene therapy in liver. Mol Ther 1:154–158
Wang L, Muramatsu S, Lu Y, Ikeguchi K, Fujimoto K, Okada T, Mizukami H, Hanazono Y, Kume A, Urano F, Ichinose H, Nagatsu T, Nakano I, Ozawa K (2002a) Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson’s disease. Gene Ther 9:381–389
Wang LJ, Lu YY, Muramatsu S, Ikeguchi K, Fujimoto K, Okada T, Mizukami H, Matsushita T, Hanazono Y, Kume A, Nagatsu T, Ozawa K, Nakano I (2002b) Neuroprotective effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis. J Neurosci 22:6920–6928
Wang C, Wang CM, Clark KR, Sferra TJ (2003) Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain. Gene Ther 10:1528–1534
Wang L, Calcedo R, Nichols TC, Bellinger DA, Dillow A, Verma IM, Wilson JM (2005a) Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy. Blood 105:3079–3086
Wang L, Cao O, Swalm B, Dobrzynski E, Herzog RW (2005b) Major role of local immune responses in antibody formation to factor IX in viral gene transfer to skeletal muscle. Gene Ther 12:1453–1464
Wang Z, Zhu T, Qiao C, Zhou L, Wang B, Zhang J, Chen C, Li J, Xiao X (2005c) Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nat Biotechnol 23:321–328
Watanabe S, Imagawa T, Boivin GP, Gao G, Wilson JM, Hirsch R (2000) Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium. Mol Ther 2:147–152
Watanabe M, Nasu Y, Kashiwakura Y, Kusumi N, Tamayose K, Nagai A, Sasano T, Shimada T, Daida H, Kumon H (2005) Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long-term maspin expression efficiently suppresses tumor growth. Hum Gene Ther 16:699–710
Watchko J, O’Day T, Wang B, Zhou L, Tang Y, Li J, Xiao X (2002) Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther 13:1451–1460
Watson GL, Sayles JN, Chen C, Elliger SS, Elliger CA, Raju NR, Kurtzman GJ, Podsakoff GM (1998) Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus. Gene Ther 5:1642–1649
Weber M, Rabinowitz J, Provost N, Conrath H, Folliot S, Briot D, Cherel Y, Chenuaud P, Samulski J, Moullier P, Rolling F (2003) Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery. Mol Ther 7:774–781
Wendtner CM, Kofler DM, Theiss HD, Kurzeder C, Buhmann R, Schweighofer C, Perabo L, Danhauser-Riedl S, Baumert J, Hiddemann W, Hallek M, Buning H (2002) Efficient gene transfer of CD40 ligand into primary B-CLL cells using recombinant adeno-associated virus (rAAV) vectors. Blood 100:1655–1661
Wilton SD, Dye DE, Laing NG (1997) Dystrophin gene transcripts skipping the mdx mutation. Muscle Nerve 20:728–734
Xia H, Mao Q, Davidson BL (2001) The HIV Tat protein transduction domain improves the biodistribution of beta-glucuronidase expressed from recombinant viral vectors. Nat Biotechnol 19:640–644
Xiao X, Li J, Samulski RJ (1996) Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol 70:8098–8108
Xiao X, Li J, Samulski RJ (1998) Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol 72:2224–2232
Xiao W, Chirmule N, Berta SC, McCullough B, Gao G, Wilson JM (1999) Gene therapy vectors based on adeno-associated virus type 1. J Virol 73:3994–4003
Xu R, Sun X, Tse LY, Li H, Chan PC, Xu S, Xiao W, Kung HF, Krissansen GW, Fan ST (2003) Long-term expression of angiostatin suppresses metastatic liver cancer in mice. Hepatology 37:1451–1460
Xu Z, Yue Y, Lai Y, Ye C, Qiu J, Pintel DJ, Duan D (2004) Trans-splicing adeno-associated viral vector-mediated gene therapy is limited by the accumulation of spliced mRNA but not by dual vector coinfection efficiency. Hum Gene Ther 15:896–905
Xu D, McCarty D, Fernandes A, Fisher M, Samulski RJ, Juliano RL (2005) Delivery of MDR1 small interfering RNA by self-complementary recombinant adeno-associated virus vector. Mol Ther 11:523–530
Yamano S, Huang LY, Ding C, Chiorini JA, Goldsmith CM, Wellner RB, Golding B, Kotin RM, Scott DE, Baum BJ (2002) Recombinant adeno-associated virus serotype 2 vectors mediate stable interleukin 10 secretion from salivary glands into the bloodstream. Hum Gene Ther 13:287–298
Yan Z, Zhang Y, Duan D, Engelhardt JF (2000) Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy. Proc Natl Acad Sci USA 97:6716–6721
Yang GS, Schmidt M, Yan Z, Lindbloom JD, Harding TC, Donahue BA, Engelhardt JF, Kotin R, Davidson BL (2002) Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size. J Virol 76:7651–7660
Yoo J, Choi S, Hwang KS, Cho WK, Jung CR, Kwon ST, Im DS (2006) Adeno-associated virus-mediated gene transfer of a secreted form of TRAIL inhibits tumor growth and occurrence in an experimental tumor model. J Gene Med 8(2):163–174
Yoshida J, Mizuno M, Nakahara N, Colosi P (2002) Antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma. Jpn J Cancer Res 93:223–228
Yoshimura M, Sakamoto M, Ikemoto M, Mochizuki Y, Yuasa K, Miyagoe-Suzuki Y, Takeda S (2004) AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype. Mol Ther 10:821–828
Yuasa K, Sakamoto M, Miyagoe-Suzuki Y, Tanouchi A, Yamamoto H, Li J, Chamberlain JS, Xiao X, Takeda S (2002) Adeno-associated virus vector-mediated gene transfer into dystrophin-deficient skeletal muscles evokes enhanced immune response against the transgene product. Gene Ther 9:1576–1588
Yue Y, Duan D (2003) Double strand interaction is the predominant pathway for intermolecular recombination of adeno-associated viral genomes. Virology 313:1–7
Yue Y, Li Z, Harper SQ, Davisson RL, Chamberlain JS, Duan D (2003) Microdystrophin gene therapy of cardiomyopathy restores dystrophin–glycoprotein complex and improves sarcolemma integrity in the mdx mouse heart. Circulation 108:1626–1632
Zabner J, Seiler M, Walters R, Kotin RM, Fulgeras W, Davidson BL, Chiorini JA (2000) Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer. J Virol 74:3852–3858
Zacchigna S, Zentilin L, Morini M, Dell’Eva R, Noonan DM, Albini A, Giacca M (2004) AAV-mediated gene transfer of tissue inhibitor of metalloproteinases-1 inhibits vascular tumor growth and angiogenesis in vivo. Cancer Gene Ther 11:73–80
Zaiss AK, Liu Q, Bowen GP, Wong NC, Bartlett JS, Muruve DA (2002) Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. J Virol 76:4580–4590
Zhang Y, Scarpace PJ (2006) Circumventing central leptin resistance: lessons from central leptin and POMC gene delivery. Peptides 27(2):350–364
Zhang JF, Hu C, Geng Y, Blatt LM, Taylor MW (1996) Gene therapy with an adeno-associated virus carrying an interferon gene results in tumor growth suppression and regression. Cancer Gene Ther 3:31–38
Zhang HG, Xie J, Yang P, Wang Y, Xu L, Liu D, Hsu HC, Zhou T, Edwards CK III, Mountz JD (2000) Adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tumor necrosis factor alpha and reduces arthritis. Hum Gene Ther 11:2431–2442
Zhong L, Chen L, Li Y, Qing K, Weigel-Kelley KA, Chan RJ, Yoder MC, Srivastava A (2004) Self-complementary adeno-associated virus 2 (AAV)-T cell protein tyrosine phosphatase vectors as helper viruses to improve transduction efficiency of conventional single-stranded AAV vectors in vitro and in vivo. Mol Ther 10:950–957
Zhu T, Zhou L, Mori S, Wang Z, McTiernan CF, Qiao C, Chen C, Wang DW, Li J, Xiao X (2005) Sustained whole-body functional rescue in congestive heart failure and muscular dystrophy hamsters by systemic gene transfer. Circulation 112:2650–2659
Ziegler RJ, Lonning SM, Armentano D, Li C, Souza DW, Cherry M, Ford C, Barbon CM, Desnick RJ, Gao GP, Wilson JM, Pelusa R, Godwin S, Carter BJ, Gergory RJ, Wadsworth SC, Cheng SH (2004) AAV2 vector harboring a liver-restricted promoter facilitates sustained expression of therapeutic levels of alpha-galactosidase A and the induction of immune tolerance in fabry mice. Mol Ther 9:231–240
Zolotukhin S (2005) Gene therapy for obesity. Expert Opin Biol Ther 5:347–357
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The authors thank Drs. Corrinna Burger, Jeffrey S. Chamberlain, Cathryn Mah for extensive assistance with the manuscript.
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Warrington, K.H., Herzog, R.W. Treatment of human disease by adeno-associated viral gene transfer. Hum Genet 119, 571–603 (2006). https://doi.org/10.1007/s00439-006-0165-6
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DOI: https://doi.org/10.1007/s00439-006-0165-6