The potential of adeno-associated viral vectors for gene delivery to muscle tissue

Expert Opinion on Drug Delivery

Volumn 11, Issue 3, 2014, Pages 345-364

  Wang, Dan ^a   Zhong, Li ^a   Nahid, M Abu ^a   Gao, Guangping ^a,b  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b SICHUAN UNIVERSITY   (China)

Author keywords

Adeno associated virus; Gene therapy; Gene transfer; Muscle

Indexed keywords

ANIMAL; DEPENDOPARVOVIRUS; GENE THERAPY; GENE TRANSFER; GENE VECTOR; GENETICS; HUMAN; METABOLISM; MUSCLE;

ANIMALS; DEPENDOVIRUS; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HUMANS; MUSCLES;

EID: 84894418067     PISSN: 17425247     EISSN: 17447593     Source Type: Journal    
DOI: 10.1517/17425247.2014.871258     Document Type: Review

References (200)

1. Blacklow NR, Hoggan MD, Rowe WP. Isolation of adenovirus-Associated viruses from man. Proc Natl Acad Sci USA 1967;58(4):1410-15
2. Gao G, Zhong L, Danos O. Exploiting natural diversity of AAV for the design of vectors with novel properties. Methods Mol Biol 2011;807:93-118
3. Muzyczka N, Berns K. Parvoviridae: The viruses and their replication. In: Knipe D, Howley P, Griffin D, et al. editors, Fields virology. Lippincott Williams and Wilkins, Philadelphia, PA; 2001. p. 2327-59
4. Grieger JC, Samulski RJ. Adeno-Associated virus vectorology, manufacturing, and clinical applications. Methods Enzymol 2012;507:229-54
5. Sonntag F, Schmidt K, Kleinschmidt JA. A viral assembly factor promotes AAV2 capsid formation in the nucleolus. Proc Natl Acad Sci USA 2010;107(22):10220-5
6. Xie Q, Bu W, Bhatia S, et al. The atomic structure of adeno-Associated virus (AAV-2), a vector for human gene therapy. Proc Natl Acad Sci USA 2002;99(16):10405-10
7. Venkatakrishnan B, Yarbrough J, Domsic J, et al. Structure and dynamics of adeno-Associated virus serotype 1 VP1-unique N-Terminal domain and its role in capsid trafficking. J Virol 2013;87(9):4974-84
8. DiMattia MA, Nam HJ, Van Vliet K, et al. Structural insight into the unique properties of adeno-Associated virus serotype 9. J Virol 2012;86(12):6947-58
9. Hoggan MD, Blacklow NR, Rowe WP. Studies of small DNA viruses found in various adenovirus preparations: Physical, biological, and immunological characteristics. Proc Natl Acad Sci USA 1966;55(6):1467-74
10. Buller RM, Janik JE, Sebring ED, et al. Herpes simplex virus types 1 and 2 completely help adenovirus-Associated virus replication. J Virol 1981;40(1):241-7
11. Schlehofer JR, Ehrbar M, zur Hausen H. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus. Virology 1986;152(1):110-17
12. Kotin RM, Siniscalco M, Samulski RJ, et al. Site-specific integration by adenoassociated virus. Proc Natl Acad Sci USA 1990;87(6):2211-15
13. Muzyczka N. Use of adeno-Associated virus as a general transduction vector for mammalian cells. Curr Top Microbiol Immunol 1992;158:97-129
14. Zhong L, Jayandharan GR, Aslanidi GV, et al. Development of novel recombinant AAV vectors and strategies for the potential gene therapy of hemophilia. J Genet Synd Gene Ther 2012;S1: Article number 008
15. Yang L, Li J, Xiao X. Directed evolution of adeno-Associated virus (AAV) as vector for muscle gene therapy. Methods Mol Biol 2011;709:127-39
16. Zhong L, Li B, Mah CS, et al. Next generation of adeno-Associated virus 2 vectors: Point mutations in tyrosines lead to high-efficiency transduction at lower doses. Proc Natl Acad Sci USA 2008;105(22):7827-32
17. McCarty DM, Fu H, Monahan PE, et al. Adeno-Associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther 2003;10(26):2112-18
18. Wang Z, Ma HI, Li J, et al. Rapid and highly efficient transduction by doublestranded adeno-Associated virus vectors in vitro and in vivo. Gene Ther 2003;10(26):2105-11
19. Smith BK, Collins SW, Conlon TJ, et al. Phase I/II trial of adeno-Associated virus-mediated alpha-glucosidase gene therapy to the diaphragm for chronic respiratory failure in Pompe disease: Initial safety and ventilatory outcomes. Hum Gene Ther 2013;24(6):630-40
20. Mingozzi F, High KA. Therapeutic in vivo gene transfer for genetic disease using AAV: Progress and challenges. Nat Rev Genet 2011;12(5):341-55
21. Bryant LM, Christopher DM, Giles AR, et al. Lessons learned from the clinical development and market authorization of Glybera. Hum Gene Ther Clin Dev 2013;24(2):55-64
22. Duan D, Sharma P, Yang J, et al. Circular intermediates of recombinant adeno-Associated virus have defined structural characteristics responsible for long-Term episomal persistence in muscle tissue. J Virol 1998;72(11):8568-77
23. Kaeppel C, Beattie SG, Fronza R, et al. A largely random AAV integration profile after LPLD gene therapy. Nat Med 2013;19(7):889-91
24. Gruntman AM, Bish LT, Mueller C, et al. Gene transfer in skeletal and cardiac muscle using recombinant adenoassociated virus. Curr Protoc Microbiol 2013; Chapter 14:Unit 14D 3
25. Miyagoe-Suzuki Y, Takeda S. Gene therapy for muscle disease. Exp Cell Res 2010;316(18):3087-92
26. Duan D, Yan Z, Yue Y, et al. Enhancement of muscle gene delivery with pseudotyped adeno-Associated virus type 5 correlates with myoblast differentiation. J Virol 2001;75(16):7662-71
27. Byrne BJ, Falk DJ, Pacak CA, et al. Pompe disease gene therapy. Hum Mol Genet 2011;20(R1):R61-8
28. Mendell JR, Rodino-Klapac L, Sahenk Z, et al. Gene therapy for muscular dystrophy: Lessons learned and path forward. Neurosci Lett 2012;527(2):90-9
29. Mah CS, Pacak CA, Byrne BJ. Muscle as a metabolic factory for gene therapy. In: Duan D, editor. Muscle gene therapy. Springer; New York, London; 2010. p. 219-30
30. Chuah MK, Evens H, VandenDriessche T. Gene therapy for hemophilia. J Thromb Haemost 2013;11(Suppl 1):99-110
31. Flotte TR, Trapnell BC, Humphries M, et al. Phase 2 clinical trial of a recombinant adeno-Associated viral vector expressing alpha1-Antitrypsin: Interim results. Hum Gene Ther 2011;22(10):1239-47
32. Rivera VM, Gao GP, Grant RL, et al. Long-Term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer. Blood 2005;105(4):1424-30
33. Fan Z, Kocis K, Valley R, et al. Safety and feasibility of high-pressure transvenous limb perfusion with 0.9% saline in human muscular dystrophy. Mol Ther 2012;20(2):456-61
34. Bowles DE, McPhee SW, Li C, et al. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther 2012;20(2):443-55
35. Bish LT, Sleeper MM, Brainard B, et al. Percutaneous transendocardial delivery of self-complementary adeno-Associated virus 6 achieves global cardiac gene transfer in canines. Mol Ther 2008;16(12):1953-9
36. Vulin A, Barthelemy I, Goyenvalle A, et al. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol Ther 2012;20(11):2120-33
37. Gao G, Bish LT, Sleeper MM, et al. Transendocardial delivery of AAV6 results in highly efficient and global cardiac gene transfer in rhesus macaques. Hum Gene Ther 2011;22(8):979-84
38. Jaski BE, Jessup ML, Mancini DM, et al. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a first-in-human phase 1/2 clinical trial. J Card Fail 2009;15(3):171-81
39. Jessup M, Greenberg B, Mancini D, et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): A phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 2011;124(3):304-13
40. Gregorevic P, Blankinship MJ, Allen JM, et al. Systemic delivery of genes to striated muscles using adeno-Associated viral vectors. Nat Med 2004;10(8):828-34
41. Wang Z, Zhu T, Qiao C, et al. Adeno-Associated virus serotype 8 efficiently delivers genes to muscle and heart. Nat Biotechnol 2005;23(3):321-8
42. Pacak CA, Sakai Y, Thattaliyath BD, et al. Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice. Genet Vaccines Ther 2008;6:13
43. Katwal AB, Konkalmatt PR, Piras BA, et al. Adeno-Associated virus serotype 9 efficiently targets ischemic skeletal muscle following systemic delivery. Gene Ther 2013;20(9):930-8
44. Yue Y, Ghosh A, Long C, et al. A single intravenous injection of adeno-Associated virus serotype-9 leads to whole body skeletal muscle transduction in dogs. Mol Ther 2008;16(12):1944-52
45. Kornegay JN, Li J, Bogan JR, et al. Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs. Mol Ther 2010;18(8):1501-8
46. Qiao C, Li J, Jiang J, et al. Myostatin propeptide gene delivery by adenoassociated virus serotype 8 vectors enhances muscle growth and ameliorates dystrophic phenotypes in mdx mice. Hum Gene Ther 2008;19(3):241-54
47. Xu L, Lu PJ, Wang CH, et al. Adeno-Associated virus 9 mediated FKRP gene therapy restores functional glycosylation of alpha-dystroglycan and improves muscle functions. Mol Ther 2013;21(10):1832-40
48. Sun B, Young SP, Li P, et al. Correction of multiple striated muscles in murine Pompe disease through adeno-Associated virus-mediated gene therapy. Mol Ther 2008;16(8):1366-71
49. Zincarelli C, Soltys S, Rengo G, et al. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther 2008;16(6):1073-80
50. Pacak CA, Mah CS, Thattaliyath BD, et al. Recombinant adeno-Associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ Res 2006;99(4):e3-9
51. Bostick B, Yue Y, Lai Y, et al. AAV-9 micro-dystrophin gene therapy ameliorates electrocardiographic abnormalities in mdx mice. Hum Gene Ther 2008;19(8):851-6
52. Goehringer C, Rutschow D, Bauer R, et al. Prevention of cardiomyopathy in delta-sarcoglycan knockout mice after systemic transfer of targeted adenoassociated viral vectors. Cardiovasc Res 2009;82(3):404-10
53. Wang Z, Zhu T, Rehman KK, et al. Widespread and stable pancreatic gene transfer by adeno-Associated virus vectors via different routes. Diabetes 2006;55(4):875-84
54. Mayra A, Tomimitsu H, Kubodera T, et al. Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles. Biochem Biophys Res Commun 2011;405(2):204-9
55. Garikipati D, Chamberlain JS. Systemic gene delivery for muscle gene therapy. In: Duan D, editor, Muscle gene therapy. Springer, New York, London; 2010. p. 163-79
56. Inagaki K, Fuess S, Storm TA, et al. Robust systemic transduction with AAV9 vectors in mice: Efficient global cardiac gene transfer superior to that of AAV8. Mol Ther 2006;14(1):45-53
57. Dong JY, Fan PD, Frizzell RA. Quantitative analysis of the packaging capacity of recombinant adeno-Associated virus. Hum Gene Ther 1996;7(17):2101-12
58. Allocca M, Doria M, Petrillo M, et al. Serotype-dependent packaging of large genes in adeno-Associated viral vectors results in effective gene delivery in mice. J Clin Invest 2008;118(5):1955-64
59. Dong B, Nakai H, Xiao W. Characterization of genome integrity for oversized recombinant AAV vector. Mol Ther 2010;18(1):87-92
60. Lai Y, Yue Y, Duan D. Evidence for the failure of adeno-Associated virus serotype 5 to package a viral genome or = 8.2 kb. Mol Ther 2010;18(1):75-9
61. Duan D, Yue Y, Yan Z, et al. A new dual-vector approach to enhance recombinant adeno-Associated virusmediated gene expression through intermolecular cis activation. Nat Med 2000;6(5):595-8
62. Duan D, Yue Y, Engelhardt JF. Expanding AAV packaging capacity with trans-splicing or overlapping vectors: A quantitative comparison. Mol Ther 2001;4(4):383-91
63. Nakai H, Storm TA, Kay MA. Increasing the size of rAAV-mediated expression cassettes in vivo by intermolecular joining of two complementary vectors. Nat Biotechnol 2000;18(5):527-32
64. Ghosh A, Yue Y, Lai Y, et al. A hybrid vector system expands adeno-Associated viral vector packaging capacity in a transgene-independent manner. Mol Ther 2008;16(1):124-30
65. Lai Y, Yue Y, Liu M, et al. Efficient in vivo gene expression by trans-splicing adeno-Associated viral vectors. Nat Biotechnol 2005;23(11):1435-9
66. Ghosh A, Yue Y, Long C, et al. Efficient whole-body transduction with transsplicing adeno-Associated viral vectors. Mol Ther 2007;15(4):750-5
67. Sun L, Li J, Xiao X. Overcoming adenoassociated virus vector size limitation through viral DNA heterodimerization. Nat Med 2000;6(5):599-602
68. Ghosh A, Yue Y, Duan D. Viral serotype and the transgene sequence influence overlapping adeno-Associated viral (AAV) vector-mediated gene transfer in skeletal muscle. J Gene Med 2006;8(3):298-305
69. Odom GL, Gregorevic P, Allen JM, et al. Gene therapy of mdx mice with large truncated dystrophins generated by recombination using rAAV6. Mol Ther 2011;19(1):36-45
70. Lopes VS, Boye SE, Louie CM, et al. Retinal gene therapy with a large MYO7A cDNA using adeno-Associated virus. Gene Ther 2013;20(8):824-33
71. Zhang Y, Duan D. Novel minidystrophin gene dual adeno-Associated virus vectors restore neuronal nitric oxide synthase expression at the sarcolemma. Hum Gene Ther 2012;23(1):98-103
72. Zhang Y, Yue Y, Li L, et al. Dual AAV therapy ameliorates exercise-induced muscle injury and functional ischemia in murine models of Duchenne muscular dystrophy. Hum Mol Genet 2013;22(18):3720-9
73. Warrington KH Jr, Gorbatyuk OS, Harrison JK, et al. Adeno-Associated virus type 2 VP2 capsid protein is nonessential and can tolerate large peptide insertions at its N terminus. J Virol 2004;78(12):6595-609
74. Grieger JC, Samulski RJ. Packaging capacity of adeno-Associated virus serotypes: Impact of larger genomes on infectivity and postentry steps. J Virol 2005;79(15):9933-44
75. Lai Y, Yue Y, Bostick B, et al. Delivering large therapeutic gene for muscle gene therapy. In: Duan D, editor, Muscle gene therapy. Springer, New York, London; 2010. p. 205-18
76. Roudaut C, Le Roy F, Suel L, et al. Restriction of calpain3 expression to the skeletal muscle prevents cardiac toxicity and corrects pathology in a murine model of limb-girdle muscular dystrophy. Circulation 2013;128(10):1094- 104
77. Falk DJ, Mah CS, Soustek MS, et al. Intrapleural administration of AAV9 improves neural and cardiorespiratory function in Pompe disease. Mol Ther 2013;21(9):1661-7
78. Toscano MG, Romero Z, Munoz P, et al. Physiological and tissue-specific vectors for treatment of inherited diseases. Gene Ther 2011;18(2):117-27
79. Cordier L, Gao GP, Hack AA, et al. Muscle-specific promoters may be necessary for adeno-Associated virusmediated gene transfer in the treatment of muscular dystrophies. Hum Gene Ther 2001;12(2):205-15
80. Salva MZ, Himeda CL, Tai PW, et al. Design of tissue-specific regulatory cassettes for high-level rAAV-mediated expression in skeletal and cardiac muscle. Mol Ther 2007;15(2):320-9
81. Lagos-Quintana M, Rauhut R, Yalcin A, et al. Identification of tissue-specific microRNAs from mouse. Curr Biol 2002;12(9):735-9
82. Brown BD, Venneri MA, Zingale A, et al. Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer. Nat Med 2006;12(5):585-91
83. Majowicz A, Maczuga P, Kwikkers KL, et al. Mir-142-3p target sequences reduce transgene directed immunogenicity following intramuscular AAV1 vectormediated gene delivery. J Gene Med 2013;15(6-7):219-32
84. Xie J, Xie Q, Zhang H, et al. MicroRNA-regulated, systemically delivered rAAV9: A step closer to CNSrestricted transgene expression. Mol Ther 2011;19(3):526-35
85. Bohl D, Salvetti A, Moullier P, et al. Control of erythropoietin delivery by doxycycline in mice after intramuscular injection of adeno-Associated vector. Blood 1998;92(5):1512-17
86. Rivera VM, Ye X, Courage NL, et al. Long-Term regulated expression of growth hormone in mice after intramuscular gene transfer. Proc Natl Acad Sci USA 1999;96(15):8657-62
87. No D, Yao TP, Evans RM. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci USA 1996;93(8):3346-51
88. Jazwa A, Florczyk U, Jozkowicz A, et al. Gene therapy on demand: Site specific regulation of gene therapy. Gene 2013;525(2):229-38
89. Apparailly F, Millet V, Noel D, et al. Tetracycline-inducible interleukin-10 gene transfer mediated by an adenoassociated virus: Application to experimental arthritis. Hum Gene Ther 2002;13(10):1179-88
90. Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet 2012;379(9813):373-83
91. Al-Khatti A, Veith RW, Papayannopoulou T, et al. Stimulation of fetal hemoglobin synthesis by erythropoietin in baboons. N Engl J Med 1987;317(7):415-20
92. Villeval JL, Rouyer-Fessard P, Blumenfeld N, et al. Retrovirus-mediated transfer of the erythropoietin gene in hematopoietic cells improves the erythrocyte phenotype in murine beta-Thalassemia. Blood 1994;84(3):928-33
93. Johnston J, Tazelaar J, Rivera VM, et al. Regulated expression of erythropoietin from an AAV vector safely improves the anemia of beta-Thalassemia in a mouse model. Mol Ther 2003;7(4):493-7
94. Herzog RW, Hagstrom JN, Kung SH, et al. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-Associated virus. Proc Natl Acad Sci USA 1997;94(11):5804-9
95. Manno CS, Chew AJ, Hutchison S, et al. AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 2003;101(8):2963-72
96. Arruda VR, Schuettrumpf J, Herzog RW, et al. 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 2004;103(1):85-92
97. Johnson PR, Schnepp BC, Zhang J, et al. Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys. Nat Med 2009;15(8):901-6
98. Balazs AB, Chen J, Hong CM, et al. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 2012;481(7379):81-4
99. Balazs AB, Bloom JD, Hong CM, et al. Broad protection against influenza infection by vectored immunoprophylaxis in mice. Nat Biotechnol 2013;31(7):647-52
100. Kessler PD, Podsakoff GM, Chen X, et al. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc Natl Acad Sci USA 1996;93(24):14082-7
101. Herzog RW, Yang EY, Couto LB, et al. Long-Term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adenoassociated viral vector. Nat Med 1999;5(1):56-63
102. Arruda VR, Hagstrom JN, Deitch J, et al. Posttranslational modifications of recombinant myotube-synthesized human factor IX. Blood 2001;97(1):130-8
103. High KA. Gene therapy for haemophilia: A long and winding road. J Thromb Haemost 2011;9(Suppl 1):2-11
104. Kay MA, Manno CS, Ragni MV, et al. Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet 2000;24(3):257-61
105. Arruda VR, Stedman HH, Haurigot V, et al. Peripheral transvenular delivery of adeno-Associated viral vectors to skeletal muscle as a novel therapy for hemophilia B. Blood 2010;115(23):4678-88
106. Lewis AD, Chen R, Montefiori DC, et al. Generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer. J Virol 2002;76(17):8769-75
107. Balazs AB, West AP Jr. Antibody gene transfer for HIV immunoprophylaxis. Nat Immunol 2013;14(1):1-5
108. Mueller C, Braag SA, Martino AT, et al. The pros and cons of immunomodulatory IL-10 gene therapy with recombinant AAV in a Cftr-/- -dependent allergy mouse model. Gene Ther 2009;16(2):172-83
109. Mingozzi F, Maus MV, Hui DJ, et al. CD8(+) T-cell responses to adenoassociated virus capsid in humans. Nat Med 2007;13(4):419-22
110. Hohlfeld R, Engel AG. The immunobiology of muscle. Immunol Today 1994;15(6):269-74
111. Nagaraju K. Immunological capabilities of skeletal muscle cells. Acta Physiol Scand 2001;171(3):215-23
112. Loell I, Lundberg IE. Can muscle regeneration fail in chronic inflammation: A weakness in inflammatory myopathies?. J Intern Med 2011;269(3):243-57
113. Garlepp MJ, Chen W, Tabarias H, et al. Antigen processing and presentation by a murine myoblast cell line. Clin Exp Immunol 1995;102(3):614-19
114. Hohlfeld R, Engel AG. Coculture with autologous myotubes of cytotoxic T cells isolated from muscle in inflammatory myopathies. Ann Neurol 1991;29(5):498-507
115. Nathwani AC, Davidoff A, Hanawa H, et al. Factors influencing in vivo transduction by recombinant adenoassociated viral vectors expressing the human factor IX cDNA. Blood 2001;97(5):1258-65
116. Mingozzi F, High KA. Immune responses to AAV vectors: Overcoming barriers to successful gene therapy. Blood 2013;122(1):23-36
117. Chirmule N, Propert K, Magosin S, et al. Immune responses to adenovirus and adeno-Associated virus in humans. Gene Ther 1999;6(9):1574-83
118. Boutin S, Monteilhet V, Veron P, et al. Prevalence of serum IgG and neutralizing factors against adeno-Associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: Implications for gene therapy using AAV vectors. Hum Gene Ther 2010;21(6):704-12
119. Calcedo R, Vandenberghe LH, Gao G, et al. Worldwide epidemiology of neutralizing antibodies to adenoassociated viruses. J Infect Dis 2009;199(3):381-90
120. High KA. The gene therapy journey for hemophilia: Are we there yet?. Hematology Am Soc Hematol Educ Program 2012;2012:375-81
121. Scallan CD, Jiang H, Liu T, et al. Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood 2006;107(5):1810-17
122. Jiang H, Couto LB, Patarroyo-White S, et al. Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood 2006;108(10):3321-8
123. Lee GK, Maheshri N, Kaspar B, et al. PEG conjugation moderately protects adeno-Associated viral vectors against antibody neutralization. Biotechnol Bioeng 2005;92(1):24-34
124. Huttner NA, Girod A, Perabo L, et al. Genetic modifications of the adenoassociated virus type 2 capsid reduce the affinity and the neutralizing effects of human serum antibodies. Gene Ther 2003;10(26):2139-47
125. Monteilhet V, Saheb S, Boutin S, et al. A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-Associated virus (AAV) types 1, 2, 6, and 8. Mol Ther 2011;19(11):2084-91
126. Mimuro J, Mizukami H, Hishikawa S, et al. Minimizing the inhibitory effect of neutralizing antibody for efficient gene expression in the liver with adenoassociated virus 8 vectors. Mol Ther 2013;21(2):318-23
127. Mingozzi F, Anguela XM, Pavani G, et al. Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med 2013;5(194):194ra92
128. Mingozzi F, High KA. Immune responses to AAV in clinical trials. Curr Gene Ther 2007;7(5):316-24
129. Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirus-Associated virus vectormediated gene transfer in hemophilia B. N Engl J Med 2011;365(25):2357-65
130. Mingozzi F, Meulenberg JJ, Hui DJ, et al. AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsidspecific T cells. Blood 2009;114(10):2077-86
131. Mendell JR, Campbell K, Rodino-Klapac L, et al. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med 2010;363(15):1429-37
132. Martino AT, Basner-Tschakarjan E, Markusic DM, et al. Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells. Blood 2013;121(12):2224-33
133. Heath WR, Carbone FR. Cross-presentation in viral immunity and self-Tolerance. Nat Rev Immunol 2001;1(2):126-34
134. Yan Z, Zak R, Luxton GW, et al. Ubiquitination of both adeno-Associated virus type 2 and 5 capsid proteins affects the transduction efficiency of recombinant vectors. J Virol 2002;76(5):2043-53
135. Pien GC, Basner-Tschakarjan E, Hui DJ, et al. Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-Associated viral vectors. J Clin Invest 2009;119(6):1688-95
136. Li C, He Y, Nicolson S, et al. Adeno-Associated virus capsid antigen presentation is dependent on endosomal escape. J Clin Invest 2013;123(3):1390-401
137. Finn JD, Hui D, Downey HD, et al. Proteasome inhibitors decrease AAV2 capsid derived peptide epitope presentation on MHC class I following transduction. Mol Ther 2010;18(1):135-42
138. Jooss K, Yang Y, Fisher KJ, et al. Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J Virol 1998;72(5):4212-23
139. Mays LE, Wilson JM. The complex and evolving story of T cell activation to AAV vector-encoded transgene products. Mol Ther 2011;19(1):16-27
140. Cresawn KO, Fraites TJ, Wasserfall C, et al. Impact of humoral immune response on distribution and efficacy of recombinant adeno-Associated virusderived acid alpha-glucosidase in a model of glycogen storage disease type II. Hum Gene Ther 2005;16(1):68-80
141. Haurigot V, Mingozzi F, Buchlis G, et al. Safety of AAV factor IX peripheral transvenular gene delivery to muscle in hemophilia B dogs. Mol Ther 2010;18(7):1318-29
142. Toromanoff A, Adjali O, Larcher T, et al. Lack of immunotoxicity after regional intravenous (RI) delivery of rAAV to nonhuman primate skeletal muscle. Mol Ther 2010;18(1):151-60
143. Wang Z, Tapscott SJ, Chamberlain JS, et al. Immunity and AAV-mediated gene therapy for muscular dystrophies in large animal models and human trials. Front Microbiol 2011;2:201
144. Sun B, Li S, Bird A, et al. Hydrostatic isolated limb perfusion with adenoassociated virus vectors enhances correction of skeletal muscle in Pompe disease. Gene Ther 2010;17(12):1500-5
145. Rodino-Klapac LR, Montgomery CL, Mendell JR, et al. AAV-mediated gene therapy to the isolated limb in rhesus macaques. Methods Mol Biol 2011;709:287-98
146. Xiao X, Li J, Samulski RJ. Production of high-Titer recombinant adeno-Associated virus vectors in the absence of helper adenovirus. J Virol 1998;72(3):2224-32
147. Yuan Z, Qiao C, Hu P, et al. A versatile adeno-Associated virus vector producer cell line method for scalable vector production of different serotypes. Hum Gene Ther 2011;22(5):613-24
148. Zhang H, Xie J, Xie Q, et al. Adenovirus-Adeno-Associated virus hybrid for large-scale recombinant adenoassociated virus production. Hum Gene Ther 2009;20(9):922-9
149. Clement N, Knop DR, Byrne BJ. Large-scale adeno-Associated viral vector production using a herpesvirus-based system enables manufacturing for clinical studies. Hum Gene Ther 2009;20(8):796-806
150. Negrete A, Yang LC, Mendez AF, et al. Economized large-scale production of high yield of rAAV for gene therapy applications exploiting baculovirus expression system. J Gene Med 2007;9(11):938-48
151. Rogers GL, Martino AT, Aslanidi GV, et al. Innate Immune Responses to AAV Vectors. Front Microbiol 2011;2:194
152. Faust SM, Bell P, Cutler BJ, et al. CpG-depleted adeno-Associated virus vectors evade immune detection. J Clin Invest 2013;123(7):2994-3001
153. Cao O, Dobrzynski E, Wang L, et al. Induction and role of regulatory CD4 +CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer. Blood 2007;110(4):1132-40
154. Lorain S, Gross DA, Goyenvalle A, et al. Transient immunomodulation allows repeated injections of AAV1 and correction of muscular dystrophy in multiple muscles. Mol Ther 2008;16(3):541-7
155. Du L, Kido M, Lee DV, et al. Differential myocardial gene delivery by recombinant serotype-specific adeno-Associated viral vectors. Mol Ther 2004;10(3):604-8
156. Palomeque J, Chemaly ER, Colosi P, et al. Efficiency of eight different AAV serotypes in transducing rat myocardium in vivo. Gene Ther 2007;14(13):989-97
157. Flotte TR, Conlon TJ, Poirier A, et al. Preclinical characterization of a recombinant adeno-Associated virus type 1-pseudotyped vector demonstrates dose-dependent injection site inflammation and dissemination of vector genomes to distant sites. Hum Gene Ther 2007;18(3):245-56
158. Ross CJ, Twisk J, Bakker AC, et al. Correction of feline lipoprotein lipase deficiency with adeno-Associated virus serotype 1-mediated gene transfer of the lipoprotein lipase S447X beneficial mutation. Hum Gene Ther 2006;17(5):487-99
159. Karakikes I, Hadri L, Rapti K, et al. Concomitant intravenous nitroglycerin with intracoronary delivery of AAV1. SERCA2a enhances gene transfer in porcine hearts. Mol Ther 2012;20(3):565-71
160. Byrne MJ, Power JM, Preovolos A, et al. Recirculating cardiac delivery of AAV2/ 1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Ther 2008;15(23):1550-7
161. Brantly ML, Chulay JD, Wang L, et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci USA 2009;106(38):16363-8
162. Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, et al. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol 2009;66(3):290-7
163. Gaudet D, Methot J, Dery S, et al. Efficacy and long-Term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: An open-label trial. Gene Ther 2013;20(4):361-9
164. Yoshimura M, Sakamoto M, Ikemoto M, et al. AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype. Mol Ther 2004;10(5):821-8
165. Zaratiegui M, Castilla-Cortazar I, Garcia M, et al. IGF1 gene transfer into skeletal muscle using recombinant adenoassociated virus in a rat model of liver cirrhosis. J Physiol Biochem 2002;58(3):169-76
166. Li J, Wang D, Qian S, et al. Efficient and long-Term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-Associated virus-2 vectors. Gene Ther 2003;10(21):1807-13
167. Tuuminen R, Nykanen AI, Krebs R, et al. PDGF-A, -C, and -D but not PDGF-B increase TGF-beta1 and chronic rejection in rat cardiac allografts. Arterioscler Thromb Vasc Biol 2009;29(5):691-8
168. Raake PW, Hinkel R, Muller S, et al. Cardio-specific long-Term gene expression in a porcine model after selective pressure-regulated retroinfusion of adenoassociated viral (AAV) vectors. Gene Ther 2008;15(1):12-17
169. Flotte TR, Brantly ML, Spencer LT, et al. Phase I trial of intramuscular injection of a recombinant adenoassociated virus alpha 1-Antitrypsin (rAAV2-CB-hAAT) gene vector to AATdeficient adults. Hum Gene Ther 2004;15(1):93-128
170. Grose WE, Clark KR, Griffin D, et al. Homologous recombination mediates functional recovery of dysferlin deficiency following AAV5 gene transfer. PLoS ONE 2012;7(6):e39233
171. Lai NC, Tang T, Gao MH, et al. Improved function of the failing rat heart by regulated expression of insulin-like growth factor I via intramuscular gene transfer. Hum Gene Ther 2012;23(3):255-61
172. Sun B, Zhang H, Franco LM, et al. Correction of glycogen storage disease type II by an adeno-Associated virus vector containing a muscle-specific promoter. Mol Ther 2005;11(6):889-98
173. Hollinger K, Gardan-Salmon D, Santana C, et al. Rescue of dystrophic skeletal muscle by PGC-1alpha involves restored expression of dystrophinassociated protein complex components and satellite cell signaling. Am J Physiol Regul Integr Comp Physiol 2013;305(1):R13-23
174. Bortolanza S, Nonis A, Sanvito F, et al. AAV6-mediated systemic shRNA delivery reverses disease in a mouse model of facioscapulohumeral muscular dystrophy. Mol Ther 2011;19(11):2055-64
175. Towne C, Raoul C, Schneider BL, et al. Systemic AAV6 delivery mediating RNA interference against SOD1: Neuromuscular transduction does not alter disease progression in fALS mice. Mol Ther 2008;16(6):1018-25
176. Rengo G, Lymperopoulos A, Zincarelli C, et al. Myocardial adenoassociated virus serotype 6-betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure. Circulation 2009;119(1):89-98
177. Pleger ST, Most P, Boucher M, et al. Stable myocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue. Circulation 2007;115(19):2506-15
178. Wang Z, Storb R, Halbert CL, et al. Successful regional delivery and longterm expression of a dystrophin gene in canine muscular dystrophy: A preclinical model for human therapies. Mol Ther 2012;20(8):1501-7
179. Bish LT, Sleeper MM, Forbes SC, et al. Long-Term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping. Mol Ther 2012;20(3):580-9
180. Bish LT, Sleeper MM, Reynolds C, et al. Cardiac gene transfer of short hairpin RNA directed against phospholamban effectively knocks down gene expression but causes cellular toxicity in canines. Hum Gene Ther 2011;22(8):969-77
181. Raake PW, Schlegel P, Ksienzyk J, et al. AAV6.betaARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur Heart J 2013;34(19):1437-47
182. Beeri R, Chaput M, Guerrero JL, et al. Gene delivery of sarcoplasmic reticulum calcium ATPase inhibits ventricular remodeling in ischemic mitral regurgitation. Circ Heart Fail 2010;3(5):627-34
183. Katz MG, Fargnoli AS, Swain JD, et al. AAV6-betaARKct gene delivery mediated by molecular cardiac surgery with recirculating delivery (MCARD) in sheep results in robust gene expression and increased adrenergic reserve. J Thorac Cardiovasc Surg 2012;143(3):720-6; e3
184. Louboutin JP, Wang L, Wilson JM. Gene transfer into skeletal muscle using novel AAV serotypes. J Gene Med 2005;7(4):442-51
185. Wang L, Louboutin JP, Bell P, et al. Muscle-directed gene therapy for hemophilia B with more efficient and less immunogenic AAV vectors. J Thromb Haemost 2011;9(10):2009-19
186. Charan RA, Niizawa G, Nakai H, et al. Adeno-Associated virus serotype 8 (AAV8) delivery of recombinant A20 to skeletal muscle reduces pathological activation of nuclear factor (NF)-kappaB in muscle of mdx mice. Mol Med 2012;18:1527-35
187. Gao MH, Lai NC, Miyanohara A, et al. Intravenous adeno-Associated virus serotype 8 encoding urocortin-2 provides sustained augmentation of left ventricular function in mice. Hum Gene Ther 2013;24(9):777-85
188. Bish LT, Morine K, Sleeper MM, et al. Adeno-Associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat. Hum Gene Ther 2008;19(12):1359-68
189. Ohshima S, Shin JH, Yuasa K, et al. Transduction efficiency and immune response associated with the administration of AAV8 vector into dog skeletal muscle. Mol Ther 2009;17(1):73-80
190. Qiao C, Li J, Zheng H, et al. Hydrodynamic limb vein injection of adeno-Associated virus serotype 8 vector carrying canine myostatin propeptide gene into normal dogs enhances muscle growth. Hum Gene Ther 2009;20(1):1-10
191. Rodino-Klapac LR, Montgomery CL, Bremer WG, et al. Persistent expression of FLAG-Tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery. Mol Ther 2010;18(1):109-17
192. Yu M, He Y, Wang K, et al. Adeno-Associated viral-mediated LARGE gene therapy rescues the muscular dystrophic phenotype in mouse models of dystroglycanopathy. Hum Gene Ther 2013;24(3):317-30
193. Karakikes I, Chaanine AH, Kang S, et al. Therapeutic cardiac-Targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling. J Am Heart Assoc 2013;2(2):e000078
194. Shin JH, Pan X, Hakim CH, et al. Microdystrophin ameliorates muscular dystrophy in the canine model of duchenne muscular dystrophy. Mol Ther 2013;21(4):750-7
195. Fish KM, Ladage D, Kawase Y, et al. AAV9.I-1c delivered via direct coronary infusion in a porcine model of heart failure improves contractility and mitigates adverse remodeling. Circ Heart Fail 2013;6(2):310-17
196. Schmidt M, Voutetakis A, Afione S, et al
197. Buj-Bello A, Fougerousse F, Schwab Y, et al. AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis. Hum Mol Genet 2008;17(14):2132-43
198. Howell JM, Walker KR, Davies L, et al. Adenovirus and adeno-Associated virusmediated delivery of human myophosphorylase cDNA and LacZ cDNA to muscle in the ovine model of McArdle's disease: Expression and reexpression of glycogen phosphorylase. Neuromuscul Disord 2008;18(3):248-58
199. Gregorevic P, Allen JM, Minami E, et al. rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice. Nat Med 2006;12(7):787-9
200. Konkalmatt PR, Beyers RJ, O'Connor DM, et al. Cardiac-selective expression of extracellular superoxide dismutase after systemic injection of adeno-Associated virus 9 protects the heart against post-myocardial infarction left ventricular remodeling. Circ Cardiov Imag 2013;6(3):478-86