Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV2-CB-hAAT) Gene Vector to AAT-Deficient Adults

Human Gene Therapy

Volumn 15, Issue 1, 2004, Pages 93-128

  Flotte, Terence R ^a   Brantly, Mark L ^a   Spencer, L Terry ^a   Byrne, Barry J ^a   Spencer, Carolyn T ^a   Baker, Dawn J ^a   Humphries, Margaret ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; ALPHA 1 ANTITRYPSIN; BETA ACTIN; HYBRID PROTEIN;

ADENO ASSOCIATED VIRUS; ADULT; ALLERGY; ALPHA 1 ANTITRYPSIN DEFICIENCY; ANAMNESIS; APPETITE DISORDER; ARTICLE; BLOOD CHEMISTRY; BLOOD SAMPLING; BLOOD TOXICITY; BONE PAIN; CHILL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYTOMEGALOVIRUS; DIARRHEA; DRUG SAFETY; DRUG SCREENING; DYSPNEA; FATIGUE; FEMALE; GENE EXPRESSION; GENE VECTOR; GENOME ANALYSIS; HEADACHE; HEMATOLOGICAL PARAMETERS; HEMATURIA; HEMOPTYSIS; HUMAN; HYPERTENSION; HYPOTENSION; IMMUNE RESPONSE; INJECTION; LIVER TOXICITY; LUNG FUNCTION TEST; LUNG INFILTRATE; LUNG TOXICITY; MALE; METABOLIC DISORDER; MYALGIA; NAUSEA; NEPHROTOXICITY; PHASE 1 CLINICAL TRIAL; PROMOTER REGION; PROTEINURIA; RESPIRATORY FAILURE; RESPIRATORY TRACT DISEASE; SEMEN ANALYSIS; SIDE EFFECT; SKIN TOXICITY; SYMPTOM; URINALYSIS; VIRAL GENE DELIVERY SYSTEM; VIRUS GENOME; VIRUS RECOMBINANT; VOMITING; WEIGHT REDUCTION; WHEEZING;

ADULT; ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; ANIMALS; CLINICAL PROTOCOLS; DEPENDOVIRUS; GENE THERAPY; GENETIC VECTORS; HUMANS; INJECTIONS, INTRAMUSCULAR; MICE;

ADENO-ASSOCIATED VIRUS; ADENOVIRIDAE; ANIMALIA; CYTOMEGALOVIRUS; GALLUS GALLUS;

EID: 0742307402     PISSN: 10430342     EISSN: None     Source Type: Journal    
DOI: 10.1089/10430340460732490     Document Type: Article

References (117)

1. Crystal, R.G. 1989. The ntitrypsin gene and its deficiency states. Trends Genet. 5:411-417.
2. Ogushi, F., R.C. Hubbard, G.A. Fells, M.A. Casolaro, D.T. Curiel, M.L. Brantly, and R.G. Crystal. 1988. Evaluation of the S-type of alpha-1-antitrypsin as an in vivo and in vitro inhibitor of neutrophil elastase. Am. Rev. Respir. Dis. 137:364-370.
3. Brantly, M.L., J.T. Wittes, C.F. Vogelmeier, R.C. Hubbard, G.A. Fells, and R.G. Crystal. 1991. Use of a highly purified alpha 1-antitrypsin standard to establish ranges for the common normal and deficient alpha 1-antitrypsin phenotypes. Chest. 100:703-708.
4. Cox, D.W., and H. Levison. 1988. Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes). Am. Rev. Respir. Dis. 137:371-375.
5. Ogushi, F., R.C. Hubbard, C. Vogelmeier, G.A. Fells, and R.G. Crystal. 1991. Risk factors for emphysema. Cigarette smoking is associated with a reduction in the association rate constant of lung alpha 1-antitrypsin for neutrophil elastase. J. Clin. Invest. 87:1060-1065.
6. Casolaro, M.A., G. Fells, M. Wewers, J.E. Pierce, F. Ogushi, R. Hubbard, S. Sellers, J. Forstrom, D. Lyons, G. Kawasaki, et al. 1987. Augmentation of lung antineutrophil elastase capacity with recombinant human alpha-1-antitrypsin. J. Appl. Physiol. 63:2015-2023.
7. Browne, R.J., D.M. Mannino, and M.J. Khoury. 1996. Alpha 1-antitrypsin deficiency deaths in the United States from 1979-1991. An analysis using multiple-cause mortality data. Chest. 110:78-83.
8. Wewers, M.D., M.A. Casolaro, S.E. Sellers, S.C. Swayze, K.M. McPhaul, J.T. Wittes, and R.G. Crystal. 1987. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N. Engl. J. Med. 316:1055-1062.
9. Wewers, M.D., M.A. Casolaro, and R.G. Crystal. 1987. Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy. Am. Rev. Respir. Dis. 135:539-543.
10. Hubbard, R.C., M.A. Casolaro, M. Mitchell, S.E. Sellers, F. Arabia, M.A. Matthay, and R.G. Crystal. 1989. Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: Use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance. Proc. Natl. Acad. Sci. U.S.A. 86:680-684.
11. Canonico, A.E., J.T. Conary, B.O. Meyrick, and K.L. Brigham. 1994. Aerosol and intravenous transfection of human alpha 1-antitrypsin gene to lungs of rabbits. Am. J. Respir. Cell Mol. Biol. 10:24-29.
12. Rosenfeld, M.A., W. Siegfried, K. Yoshimura, K. Yoneyama, M. Fukayama, L.E. Stier, P.K. Paakko, P. Gilardi, L.D. Stratford-Perricaudet, M. Perricaudet, et al. 1991. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo [see comments]. Science 252:431-434.
13. Setoguchi, Y., H.A. Jaffe, C.S. Chu, and R.G. Crystal. 1994. Intraperitoneal in vivo gene therapy to deliver alpha 1-antitrypsin to the sys temic circulation. Am. J. Respir. Cell Mol. Biol. 10:369-377.
14. Alino, S.F., M. Bobadilla, J. Crespo, and M. Lejarreta. 1996. Human alpha 1-antitrypsin gene transfer to in vivo mouse hepatocytes. Hum. Gene Ther. 7:531-536.
15. Kay, M.A., F. Graham, F. Leland, and S.L. Woo. 1995. Therapeutic serum concentrations of human alpha-1-antitrypsin after adenoviral-mediated gene transfer into mouse hepatocytes. Hepatology 21:815-819.
16. Alino, S.F., J. Crespo, M. Bobadilla, M. Lejarreta, C. Blaya, and A. Crespo. 1994. Expression of human alpha 1-antitrypsin in mouse after in vivo gene transfer to hepatocytes by small liposomes. Biochem. Biophys. Res. Commun. 204:1023-1030.
17. Crepso, J., C. Blaya, A. Crespo, and S.F. Alino. 1996. Long-term expression of the human alpha 1-antitrypsin gene in mice employing an-ionic and cationic liposome vectors. Biochem. Pharmacol. 51:1309-1314.
18. Setoguchi, Y., H.A. Jaffe, C. Danel, and R.G. Crystal. 1994. Ex vivo and in vivo gene transfer to the skin using replication-deficient recombinant adenovirus vectors. J. Invest. Dermatol. 102:415-421.
19. Kay, M.A., Q. Li, T.J. Liu, F. Leland, C. Toman, M. Finegold, and S.L. Woo. 1992. Hepatic gene therapy: persistent expression of human alpha 1-antitrypsin in mice after direct gene delivery in vivo. Hum. Gene Ther. 3:641-647.
20. Kay, M.A., P. Baley, S. Rothenberg, F. Leland, L. Fleming, K.P. Ponder, T. Liu, M. Finegold, G. Darlington, W. Pokorny, et al. 1992. Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. Proc. Natl. Acad. Sci. U.S.A. 89:89-93.
21. Levy, M.Y., L.G. Barron, K.B. Meyer, and F.C. Szoka, Jr. 1996. Characterization of plasmid DNA transfer into mouse skeletal muscle: Evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Ther. 3:201-211.
22. Meyer, K.B., M.M. Thompson, M.Y. Levy, L.G. Barron, and F.C. Szoka, Jr. 1995. Intratracheal gene delivery to the mouse airway: Characterization of plasmid DNA expression and pharmacokinetics. Gene Ther. 2:450-460.
23. Qiu, P., P. Ziegelhoffer, J. Sun, and N.S. Yang. 1996. Gene gun delivery of mRNA in situ results in efficient transgene expression and genetic immunization. Gene Ther. 3:262-268.
24. Guo, Z.S., L.H. Wang, R.C. Eisensmith, and S.L. Woo. 1996. Evaluation of promoter strength for hepatic gene expression in vivo following adenovirus-mediated gene transfer. Gene Ther. 3:802-810.
25. Schiedner, G., N. Mortal, R.J. Parks, Y. Wu, S.C. Koopmans, C. Langston, F.L. Graham, A.L. Beaudet, and S. Kochanek. 1998. Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity [published erratum appears in Nat Genet 1998;18:298]. Nat. Genet. 18:180-183.
26. Song, S., M. Morgan, T. Ellis, A. Poirier, K. Chesnut, J. Wang, M. Brantly, N. Muzyczka, B.J. Byrne, M. Atkinson, and T.R. Flotte. 1998. Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc. Natl. Acad. Sci. U.S.A. 95:14384-14388.
27. Flotte, T.R., S.A. Afione, C. Conrad, S.A. McGrath, R. Solow, H. Oka, P.L. Zeitlin, W.B. Guggino, and B.J. Carter. 1993. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc. Natl. Acad. Sci. U.S.A. 90:10613-10617.
28. Kaplitt, M.G., P. Leone, R.J. Samulski, X. Xiao, D.W. Pfaff, K.L. O'Malley, and M.J. During. 1994. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat. Genet. 8:148-154.
29. Flannery, J.G., S. Zolotukhin, M.I. Vaquero, M.M. LaVail, N. Muzyczka, and W.W. Hauswirth. 1997. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc. Natl. Acad. Sci. U.S.A. 94:6916-6921.
30. Zolotukhin, S., M. Potter, W.W. Hauswirth, J. Guy, and N. Muzyczka. 1996. A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J. Virol. 70:4646-4654.
31. Peel, A.L., S. Zolotukhin, G.W. Schrimsher, N. Muzyczka, and P.J. Reier. 1997. Efficient transduction of green fluorescent protein in spinal cord neurons using adeno-associated virus vectors containing cell type-specific promoters. Gene Ther. 4:16-24.
32. Snyder, R.O., C.H. Miao, G.A. Patijn, S.K. Spratt, O. Danos, D. Nagy, A.M. Gown, B. Winther, L. Meuse, L.K. Cohen, A.R. Thompson, and M.A. Kay. 1997. Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors. Nat. Genet. 16:270-276.
33. Fisher, K.J., K. Jooss, J. Alston, Y. Yang, S.E. Haecker, K. High, R. Pathak, S.E. Raper, and J.M. Wilson. 1997. Recombinant adeno-associated virus for muscle directed gene therapy. Nat. Med. 3:306-312.
34. Kessler, P.D., G.M. Podsakoff, X. Chen, S.A. McQuiston, P.C. Colosi, L.A. Matelis, G.J. Kurtzman, and B.J. Byrne. 1996. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc. Natl. Acad. Sci. U.S.A. 93:14082-14087.
35. Xiao, X., J. Li, and R.J. Samulski. 1996. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J. Virol. 70:8098-8108.
36. Conrad, C.K., S.S. Allen, S.A. Afione, T.C. Reynolds, S.E. Beck, M. Fee-Maki, X. Barrazza-Ortiz, R. Adams, F.B. Askin, B.J. Carter, W.B. Guggino, and T.R. Flotte. 1996. Safety of single-dose administration of an adeno-associated virus (AAV)-CFTR vector in the primate lung. Gene Ther. 3:658-668.
37. Afione, S.A., C.K. Conrad, W.G. Kearns, S. Chunduru, R. Adams, T.C. Reynolds, W.B. Guggino, G.R. Cutting, B.J. Carter, and T.R. Flotte. 1996. In vivo model of adeno-associated virus vector persistence and rescue. J. Virol. 70:3235-3241.
38. Egan, M., T. Flotte, S. Afione, R. Solow, P.L. Zeitlin, B.J. Carter, and W.B. Guggino. 1992. Defective regulation of outwardly rectifying Cl-channels by protein kinase A corrected by insertion of CFTR [see comments]. Nature 358:581-584.
39. Flotte, T.R., S.A. Afione, R. Solow, M.L. Drumm, D. Markakis, W.B. Guggino, P.L. Zeitlin, and B.J. Carter. 1993. Expression of the cystic fibrosis transmembrane conductance regulator from a novel adeno-associated virus promoter. J. Biol. Chem. 268:3781-3790.
40. Schwiebert, E.M., T. Flotte, G.R. Cutting, and W.B. Guggino. 1994. Both CFTR and outwardly rectifying chloride channels contribute to cAMP-stimulated whole cell chloride currents. Am. J. Physiol. 266:C1464-C1477.
41. Flotte, T., B. Carter, C. Conrad, W. Guggino, T. Reynolds, B. Rosenstein, G. Taylor, S. Walden, and R. Wetzel. 1996. A phase I study of an adeno-associated virus-CFTR gene vector in adult CF patients with mild lung disease. Hum. Gene Ther. 7:1145-1159.
42. Wagner, J.A., A.H. Messner, M.L. Moran, R. Daifuku, K. Kouyama, J.K. Desch, S. Manley, A.M. Norbash, C.K. Conrad, S. Friborg, T. Reynolds, W.B. Guggino, R.B. Moss, B.J. Carter, J.J. Wine, T.R. Flotte, and P. Gardner. 1999. Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane conductance regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Laryngoscope 109:266-274.
43. Wagner J.A., T. Reynolds, M.L. Moran, R.B. Moss, J.J. Wine, T.R. Flotte, and P. Gardner. 1998. Efficient and persistent gene transfer of AAV-CFTR in the CF maxillary sinus. Lancet. 351:1702-1703.
44. Virella-Lowell, I., A. Poirier, K.A. Chesnut, M. Brantly, and T.R. Flotte. 2000. Inhibition of recombinant adeno-associated virus (rAAV) transduction by bronchial secretions from cystic fibrosis patients. Gene Ther. 7:1783-1789.
45. Kang, H.A., J.H. Sohn, E.S. Choi, B.H. Chung, M.H. Yu, and S.K. Rhee. 1998. Glycosylation of human alpha 1-antitrypsin in Saccharomyces cerevisiae and methylotrophic yeasts. Yeast 14:371-381.
46. Tebbutt, S.J. 2000. Technology evaluation: Transgenic alpha 1-antitrypsin (AAT), PPL therapeutics. Curr. Opin. Mol. Ther. 2:199-204.
47. Donsante, A., C. Vogler, N. Muzyczka, J.M. Crawford, J. Barker, T. Flotte, M. Campbell-Thompson, T. Daly, and M.S. Sands. 2001. Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors. Gene Ther. 8:1343-1346.
48. Song, S., J. Embury, P.J. Laipis, K.I. Berns, J.M. Crawford, and T.R. Flotte. 2001. Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal vein injection of recombinant adeno-associated virus (rAAV) vectors. Gene Ther. 8:1299-1306.
49. Carter, B.J., G. Khoury, and D.T. Denhardt. 1975. Physical map and strand polarity of specific fragments of adenovirus-associated virus DNA produced by endonuclease R-EcoRI. J. Virol. 16:559-568.
50. Muzyczka, N., R.J. Samulski, P. Hermonat, A. Srivastava, and K.I. Berns. 1984. The genetics of adeno-associated virus. Adv. Exp. Med. Biol. 179:151-161.
51. Atchison, R.W., B.C. Casto, and W.M. Hammon. 1966. Electron microscopy of adenovirus-associated virus (AAV) in cell cultures. Virology 29:353-357.
52. Hoggan, M.D., N.R. Blacklow, and W.P. Rowe. 1966. Studies of small DNA viruses found in various adenovirus preparations: Physical, biological, and immunological characteristics. Proc. Natl. Acad. Sci. U.S.A. 55:1467-1474.
53. Hoggan, M.D., A.J. Shatkin, N.R. Blacklow, F. Koczot, and J.A. Rose. 1968. Helper-dependent infectious deoxyribonucleic acid from adenovirus-associated virus. J. Virol. 2:850-851.
54. Blacklow, N.R., M.D. Hoggan, and W.P. Rowe. 1967. Isolation of adenovirus-associated viruses from man. Proc. Natl. Acad. Sci. U.S.A. 58:1410-1415.
55. Blacklow, N.R., M.D. Hoggan, and W.P. Rowe. 1968. Serologic evidence for human infection with adenovirus-associated viruses. J. Natl. Cancer Inst. 40:319-327.
56. Blacklow, N.R., R. Dolin, and M.D. Hoggan. 1971. Studies of the enhancement of an adenovirus-associated virus by herpes simplex virus. J. Gen. Virol. 10:29-36.
57. Blacklow, N.R., M.D. Hoggan, A.Z. Kapikian, J.B. Austin, and W.P. Rowe. 1968. Epidemiology of adenovirus-associated virus infection in a nursery population. Am. J. Epidemiol. 88:368-378.
58. Flotte, T.R., and B.J. Carter. 1995. Adeno-associated virus vectors for gene therapy. Gene Ther. 2:357-362.
59. Berns, K.I., and R.M. Linden. 1995. The cryptic life style of adeno-associated virus. Bioessays 17:237-245.
60. Summerford, C., and R.J. Samulski. 1998. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J. Virol. 72:1438-1445.
61. Qing, K., C. Mah, J. Hansen, S. Zhou, V. Dwarki, and A. Srivastava. 1999. Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2 [In Process Citation]. Nat. Med. 5:71-77.
62. Summerford, C., J.S. Bartlett, and R.J. Samulski. 1999. AlphaVbeta5 integrin: A co-receptor for adeno-associated virus type 2 infection. Nat. Med. 5:78-82.
63. Berns, K.I., T.C. Pinkerton, G.F. Thomas, and M.D. Hoggan. 1975. Detection of adeno-associated virus (AAV)-specific nucleotide sequences in DNA isolated from latently infected Detroit 6 cells. Virology 68:556-560.
64. Cheung, A.K., M.D. Hoggan, W.W. Hauswirth, and K.I. Berns. 1980. Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. J. Virol. 33:739-748.
65. Kotin, R.M., M. Siniscalco, R.J. Samulski, X.D. Zhu, L. Hunter, C.A. Laughlin, S. McLaughlin, N. Muzyczka, M. Rocchi, and K.I. Berns. 1990. Site-specific integration by adeno-associated virus. Proc. Natl. Acad. Sci. U.S.A. 87:2211-2215.
66. Kotin, R.M., J.C. Menninger, D.C. Ward, and K.I. Berns. 1991. Mapping and direct visualization of a region-specific viral DNA integration site on chromosome 19q13-qter. Genomics 10:831-834.
67. Kotin, R.M., R.M. Linden, and K.I. Berns. 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.
68. Samulski, R.J., X. Zhu, X. Xiao, J.D. Brook, D.E. Housman, N. Epstein, and L.A. Hunter. 1991. Targeted integration of adeno-associated virus (AAV) into human chromosome 19 [published erratum appears in EMBO J 1992;11:1228]. EMBO J 10:3941-3950.
69. Samulski, R.J. 1993. Adeno-associated virus: Integration at a specific chromosomal locus. Curr. Opin. Genet. Dev. 3:74-80.
70. Weitzman, M.D., S.R. Kyostio, R.M. Kotin, and R.A. Owens. 1994. Adeno-associated virus (AAV) Rep proteins mediate complex formation between AAV DNA and its integration site in human DNA. Proc. Natl. Acad. Sci. U.S.A. 91:5808-5812.
71. Giraud, C., E. Winocour, and K.I. Berns. 1994. Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence. Proc. Natl. Acad. Sci. U.S.A. 91:10039-10043.
72. Giraud, C., E. Winocour, and K.I. Berns. 1995. Recombinant junctions formed by site-specific integration of adeno-associated virus into an episome. J. Virol. 69:6917-6924.
73. Linden, R.M., P. Ward, C. Giraud, E. Winocour, and K.I. Berns. 1996. Site-specific integration by adeno-associated virus. Proc. Natl. Acad. Sci. U.S.A. 93:11288-11294.
74. Hoggan, M., G. Thomas, F. Thomas, and F. Johnson. 1972. Presented at the 4th Lepetit Colloquium, Cocoyac, Mexico.
75. Kearns, W.G., S.A. Afione, S.B. Fulmer, M.C. Pang, D. Erikson, M. Egan, M.J. Landrum, T.R. Flotte, and G.R. Cutting. 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.
76. Flotte, T.R., S.A. Afione, and P.L. Zeitlin. 1994. Adeno-associated virus vector gene expression occurs in nondividing cells in the absence of vector DNA integration. Am. J. Respir. Cell. Mol. Biol. 11:517-521.
77. Senapathy, P., J.D. Tratschin, and B.J. Carter. 1984. Replication of adeno-associated virus DNA. Complementation of naturally occurring rep-mutants by a wild-type genome or an ori-mutant and correction of terminal palindrome deletions. J. Mol. Biol. 179:1-20.
78. Im, D.S., and N. Muzyczka. 1990. The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell 61:447-457.
79. Pereira, D.J., and N. Muzyczka. 1997. The cellular transcription factor SP1 and an unknown cellular protein are required to mediate Rep protein activation of the adeno-associated virus p19 promoter. J. Virol. 71:1747-1756.
80. Pereira, D.J., D.M. McCarty, and N. Muzyczka. 1997. The adeno-associated virus (AAV) Rep protein acts as both a repressor and an activator to regulate AAV transcription during a productive infection. J. Virol. 71:1079-1088.
81. Trempe, J.P., and B.J. Carter. 1988. Alternate mRNA splicing is required for synthesis of adeno-associated virus VP1 capsid protein. J. Virol. 62:3356-3363.
82. Wu, P., W. Xiao, T. Conlon, J. Hughes, M. Agbandje-McKenna, T. Ferkol, T. Flotte, and N. Muzyczka. 2000. Mutational analysis of the adeno-associated virus type 2 (AAV2) capsid gene and construction of AAV2 vectors with altered tropism [In Process Citation]. J. Virol. 74:8635-8647.
83. Tratschin, J.D., M.H. West, T. Sandbank, and B.J. Carter. 1984. 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.
84. Rolling, F., W.Y. Shen, H. Tabarias, I. Constable, Y. Kanagasingam, C.J. Barry, and P.E. Rakoczy. 1999. Evaluation of adeno-associated virus-mediated gene transfer into the rat retina by clinical fluorescence photography. Hum. Gene Ther. 10:641-648.
85. Flotte, T.R., R. Solow, R.A. Owens, S. Afione, P.L. Zeitlin, and B.J. Carter. 1992. Gene expression from adeno-associated virus vectors in airway epithelial cells. Am. J. Respir. Cell. Mol. Biol. 7:349-356.
86. Dong, J.Y., P.D. Fan, and R.A. Frizzell. 1996. Quantitative analysis of the packaging capacity of recombinant adeno-associated virus. Hum. Gene Ther. 7:2101-2112.
87. Xiao, X., J. Li, and R.J. Samulski. 1998. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J. Virol. 72:2224-2232.
88. Li, J., R.J. Samulski, and X. Xiao. 1997. Role for highly regulated rep gene expression in adeno-associated virus vector production. J. Virol. 71:5236-5243.
89. Clark, K.R., F. Voulgaropoulou, and P.R. Johnson. 1996. A stable cell line carrying adenovirus-inducible rep and cap genes allows for infectivity titration of adeno-associated virus vectors. Gene Ther. 3:1124-1132.
90. Flotte, T.R., X. Barraza-Ortiz, R. Solow, S.A. Afione, B.J. Carter, and W.B. Guggino. 1995. An improved system for packaging recombinant adeno-associated virus vectors capable of in vivo transduction. Gene Ther. 2:29-37.
91. Gao, G.P., G. Qu, L.Z. Faust, R.K. Engdahl, W. Xiao, J.V. Hughes, P.W. Zoltick, and J.M. Wilson. 1998. High-titer adeno-associated viral vectors from a Rep/Cap cell line and hybrid shuttle virus. Hum. Gene Ther. 9:2353-2362.
92. Zolotukhin, S., B.J. Byrne, E. Mason, I. Zolotukhin, M. Potter, K. Chesnut, C. Summerford, R.J. Samulski, and N. Muzyczka. 1999. Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Therapy 6:973-985.
93. Flotte, T.R., S.A. Afione, C. Conrad, S.A. McGrath, R. Solow, H. Oka, P.L. Zeitlin, W.B. Guggino, and B.J. Carter. 1993. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc. Natl. Acad. Sci. U.S.A. 90:10613-10617.
94. Conrad, C.K., S.S. Allen, S.A. Afione, T.C. Reynolds, S.E. Beck, M. Fee-Maki, X. Barrazza-Ortiz, R. Adams, F.B. Askin, B.J. Carter, W.B. Guggino, and T.R. Flotte. 1996. Safety of single-dose administration of an adeno-associated virus (AAV)-CFTR vector in the primate lung. Gene Ther. 3:658-668.
95. Flotte, T.R., and B.J. Carter. 1998. Adeno-associated virus vectors for gene therapy of cystic fibrosis. Meth. Enzymol. 292:717-732.
96. Beck, S.E., L.A. Jones, K. Chesnut, S.M. Walsh, T.C. Reynolds, B.J. Carter, F.B. Askin, T.R. Flotte, and W.B. Guggino. 1999. Repeated delivery of adeno-associated virus vectors to the rabbit airway. J. Virol. 73:9446-9455.
97. Hernandez, Y.J., J. Wang, W.G. Kearns, S. Loiler, A. Poirier, and T.R. Flotte. 1999. Latent adeno-associated virus infection elicits humoral but not cell-mediated immune responses in a nonhuman primate model [In Process Citation]. J. Virol. 73:8549-8558.
98. Jooss, K., Y. Yang, K.J. Fisher, and J.M. Wilson. 1998. Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J. Virol. 72:4212-4223.
99. Kaplitt, M.G., P. Leone, R.J. Samulski, X. Xiao, D.W. Pfaff, K.L. O'Malley, and M.J. During. 1994. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat. Genet. 8:148-154.
100. McCown, T.J., X. Xiao, J. Li, G.R. Breese, and R.J. Samulski. 1996. Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res. 713:99-107.
101. Tebbutt, S.J. 2000. Technology evaluation: Transgenic alpha-1-antitrypsin (AAT), PPL therapeutics. Curr. Opin. Mol. Ther. 2:199-204.
102. Mandel, R.J., S.K. Spratt, R.O. Snyder, and S.E. Leff. 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. U.S.A. 94:14083-14088.
103. Xiao, X., J. Li, and R.J. Samulski. 1996. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J. Virol. 70:8098-8108.
104. Kessler, P.D., G.M. Podsakoff, X. Chen, S.A. McQuiston, P.C. Colosi, L.A. Matelis, G.J. Kurtzman, and B.J. Byrne. 1996. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc. Natl. Acad. Sci. U.S.A. 93:14082-14087.
105. Clark, K.R., T.J. Sferra, and P.R. Johnson. 1997. Recombinant adeno-associated viral vectors mediate long-term transgene expression in muscle. Hum. Gene Ther. 8:659-669.
106. Fisher, K.J., K. Jooss, J. Alston, Y. Yang, S.E. Haecker, K. High, R. Pathak, S.E. Raper, and J.M. Wilson. 1997. Recombinant adeno-associated virus for muscle directed gene therapy. Nat. Med. 3:306-312.
107. Song, S., M. Morgan, T. Ellis, A. Poirier, K. Chesnut, J. Wang, M. Brantly, N. Muzyczka, B.J. Byrne, M. Atkinson, and T.R. Flotte. 1998. Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc. Natl. Acad. Sci. U.S.A. 95:14384-14388.
108. Flannery, J.G., S. Zolotukhin, M.I. Vaquero, M.M. LaVail, N. Muzyczka, and W.W. Hauswirth. 1997. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc. Natl. Acad. Sci. U.S.A. 94:6916-6921.
109. Lewin, A.S., K.A. Drenser, W.W. Hauswirth, S. Nishikawa, D. Yasumura, J.G. Flannery, and M.M. LaVail. 1998. Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa [published erratum appears in Nat. Med. 1998;4:1081]. Nat. Med. 4:967-971.
110. Zolotukhin, S., M. Potter, W.W. Hauswirth, J. Guy, and N. Muzyczka. 1996. A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J. Virol. 70:4646-4654.
111. Rolling, F., W.Y. Shen, H. Tabarias, I. Constable, Y. Kanagasingam, C.J. Barry, and P.E. Rakoczy. 1999. Evaluation of adeno-associated virus-mediated gene transfer into the rat retina by clinical fluorescence photography. Hum. Gene Ther. 10:641-648.
112. Song, S., P.J. Laipis, K.I. Berns, and T.R. Flotte. 2001. Effect of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle. Proc. Natl. Acad. Sci. U.S.A. 98:4084-4088.
113. Tratschin, J.D., I.L. Miller, and B.J. Carter. 1984. 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.
114. Halbert, C.L., T.A. Standaert, C.B. Wilson, and A.D. Miller. 1998. Successful readministration of adeno-associated virus vectors to the mouse lung requires transient immunosuppression during the initial exposure. J. Virol. 72:9795-9805.
115. Summerford, C., and R.J. Samulski. 1998. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J. Virol. 72:1438-1445.
116. Poirier, A., M. Campbell-Thompson, Q. Tang, M. Scott-Jorgensen, L. Combee, S. Loiler, J. Crawford, S. Song, and T.R. Flotte. 2003. Toxicology and biodistribution studies of a recombinant adeno-associated virus 2 (rAAV2)-Alpha-1 antitrypsin (AAT) vector. PreClinica (in Press).
117. Song, S., M. Scott-Jorgensen, J. Wang, A. Poirier, J. Crawford, M. Campbell-Thompson, and T.R. Flotte. 2002. Intramuscular administration of recombinant adeno-associated virus 2-alpha 1-antitrypsin (rAAV-AAT) vectors in a non-human primate model: Safety and immunologic aspects. Mol. Ther. 6:329-335.