Gene replacement therapies for Duchenne muscular dystrophy using adeno-associated viral vectors

Current Gene Therapy

Volumn 12, Issue 3, 2012, Pages 139-151

  Seto, Jane T ^a   Ramos, Julian N ^a   Muir, Lindsey ^a   Chamberlain, Jeffrey S ^a,b   Odom, Guy L ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Adeno associated viral vector; Duchenne muscular dystrophy; Dystrophin; Gene therapy; Immune response; Micro dystrophin; Micro utrophin

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; DYSTROPHIN; PARVOVIRUS VECTOR; PLASMID DNA; UTROPHIN;

ADENO ASSOCIATED VIRUS; BECKER MUSCULAR DYSTROPHY; CLINICAL PRACTICE; CYTOTOXIC T LYMPHOCYTE; DUCHENNE MUSCULAR DYSTROPHY; GENE MUTATION; GENE REPLACEMENT THERAPY; GENE TARGETING; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOTOXICITY; MUSCULAR DYSTROPHY; NONHUMAN; REVIEW; STEM CELL; VIRAL GENE DELIVERY SYSTEM; VIRION; VIRUS CAPSID;

DEPENDOVIRUS; DYSTROPHIN; GENE EXPRESSION; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HUMANS; IMMUNITY, ACTIVE; MUSCULAR DYSTROPHY, DUCHENNE; MUTATION;

EID: 84862631856     PISSN: 15665232     EISSN: 18755631     Source Type: Journal    
DOI: 10.2174/156652312800840603     Document Type: Review

References (195)

1. Aartsma-Rus A, Fokkema I, Verschuuren J, et al. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat 2009; 30: 293-299.
2. Adriouch S, Franck E, Drouot L, et al. Improved immunological tolerance following combination therapy with CTLA-4/Ig and AAV-mediated PD-L1/2 muscle gene transfer. Front Microbiol 2011; 2: 199.
3. Akache B, Grimm D, Pandey K, Yant SR, Xu H, Kay MA. The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9. J Virol 2006; 80: 9831-9836.
4. Akache B, Grimm D, Shen X, et al. A two-hybrid screen identifies cathepsins B and L as uncoating factors for adeno-associated virus 2 and 8. Mol Ther 2007; 15: 330-9.
5. Aoki Y, Nakamura A, Yokota T, et al. In-frame dystrophin following exon 51-skipping improves muscle pathology and function in the exon 52-deficient mdx mouse. Mol Ther 2010; 18: 1995-2005.
6. Araki E, Nakamura K, Nakao K, et al. Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy. Biochem Biophys Res Commun 1997; 238: 492-7.
7. Arnett AL, Chamberlain JR, Chamberlain JS. Therapy for neuromuscular disorders. Curr Opin Genet Dev 2009; 19: 290-7.
8. Arnett AL, Ramos JN, Chamberlain JS. Viral Gene Therapy. In: Hill JA, and Olson E, Eds. Skeletal Muscle: Fundamental Biology and Mechanisms of Disease. USA; Elsevier 2012, in press.
9. Arnett ALH, Garikipati D, Wang Z, Tapscott SJ, Chamberlain JS. Immune responses to rAAV6: The influence of canine parvovirus vaccination and neonatal administration of viral vector. Front Microbiol 2011; 2: 220.
10. Asokan A, Hamra JB, Govindasamy L, Agbandje-McKenna M, Samulski RJ. Adeno-associated virus type 2 contains an integrin alpha 5 beta 1 binding domain essential for viral cell entry. J Virol 2006; 80: 8961-9.
11. Atchison RW, Casto BC, Hammon WM. Adenovirus-Associated Defective Virus Particles. Science 1965; 149: 754-6.
12. Banks GB, Chamberlain JS, Froehner SC. Truncated dystrophins can influence neuromuscular synapse structure. Mol Cell Neurosci 2009; 40: 433-41.
13. Banks GB, Combs AC, Chamberlain JR, Chamberlain JS. Molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a truncated dystrophin. Hum Mol Genet 2008; 17: 3975-86.
14. Banks GB, Gregorevic P, Allen JM, Finn EE, Chamberlain JS. Functional capacity of dystrophins carrying deletions in the N-terminal actin-binding domain. Hum Mol Genet 2007; 16: 2105-13.
15. Banks GB, Judge LM, Allen JM, Chamberlain JS. The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins. PLoS Genet 2010; 6: e1000958.
16. Bartel M, Schaffer D, Büning H. Enhancing the clinical potential of AAV vectors by capsid engineering to evade pre-existing immunity. Front Microbiol 2011; 2: 204
17. Bartel MA, Weinstein JR, Schaffer DV. Directed evolution of novel adeno-associated viruses for therapeutic gene delivery. Gene Ther 2012; 19: 162-8.
18. Bartlett JS, Wilcher R, Samulski RJ. Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors. J Virol 2000; 74: 2777-85.
19. Beggs AH, Hoffman EP, Snyder JR, et al. Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Am J Hum Genet 1991; 49: 54-67.
20. Berns KI. Parvovirus replication. Microbiological reviews 1990; 54: 316-29.
21. Berns KI, Giraud C: Biology of adeno-associated virus. Curr Top Microbiol Immunol 1996; 218: 1-23.
22. Bhosle RC, Michele DE, Campbell KP, Li Z, Robson RM. Interactions of intermediate filament protein synemin with dystrophin and utrophin. Biochem Biophys Res Commun 2006; 346: 768-77.
23. Blake DJ, Weir A, Newey SE, Davies KE. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 2002; 82: 291-329.
24. Blankinship M, Gregorevic P, Chamberlain J. Gene Therapy of Muscular Dystrophy Using Adeno-Associated Viral Vectors: Promises and Limitations. In: eds, Chamberlain J and Rando, T. Duchenne Muscular Dystrophy: Adv Ther Inform Healthcare, (2006), pp. 413-38.
25. Bleker S, Sonntag F, Kleinschmidt JA. Mutational analysis of narrow pores at the fivefold symmetry axes of adeno-associated virus type 2 capsids reveals a dual role in genome packaging and activation of phospholipase A2 activity. J Virol 2005; 79: 2528-40.
26. 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: 704-12.
27. 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: 443-455.
28. Brenman JE, Chao DS, Xia H, Aldape K, Bredt DS. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 1995; 82: 743-52.
29. Brister JR, Muzyczka N. Mechanism of Rep-mediated adeno-associated virus origin nicking. J Virol 2000; 74: 7762-71.
30. Brockstedt DG, Podsakoffc GM, Fonga L, et al. Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration. Clin Immunol 1999; 92: 67-75.
31. Brown BD, Gentner B, Cantore A, et al. Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotech 2007; 25: 1457-67.
32. Bulfield G, Siller WG, Wight PA, Moore KJ. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci U S A 1984; 81: 1189-92.
33. Campbell KP, Knudson CM, Imagawa T, et al. Identification and characterization of the high affinity [3H]ryanodine receptor of the junctional sarcoplasmic reticulum Ca2+ release channel. J Biol Chem 1987; 262: 6460-3.
34. Cerletti M, Negri T, Cozzi F, et al. Dystrophic phenotype of canine X-linked muscular dystrophy is mitigated by adenovirus-mediated utrophin gene transfer. Gene Ther 2003; 10: 750-7.
35. Chamberlain JR, Chamberlain JS. Muscling in: Gene therapies for muscular dystrophy target RNA. Nat Med 2010; 16: 170-1. [36] Chamberlain JS. Duchenne muscular dystrophy models show their age. Cell 2010; 143: 1040-2.
36. Chamberlain JS, Metzger J, Reyes M, Townsend D, Faulkner JA. Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma. FASEB J 2007; 21: 2195-204.
37. Chao H, Liu Y, Rabinowitz J, et al. Several log increase in therapeutic transgene delivery by distinct adeno-associated viral serotype vectors. Molecular therapy: J Am Soc Gene Ther 2000; 2: 619-23.
38. Chapman VM, Miller DR, Armstrong D, Caskey CT. Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. Proc Natl Acad Sci U S A 1989; 86: 1292-6.
39. Chirmule N, Xiao W, Truneh A, et al. Humoral immunity to adeno-associated virus type 2 vectors following administration to murine and nonhuman primate muscle. J Virol 2000; 74: 2420-5.
40. Cirak S, Arechavala-Gomeza V, Guglieri M, et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 2011; 378: 595-605.
41. Collaco RF, Kalman-Maltese V, Smith AD, Dignam JD, Trempe JP. A biochemical characterization of the adeno-associated virus Rep40 helicase. J Biol Chem 2003; 278: 34011-7.
42. Cooper BJ, Winand NJ, Stedman H, et al. The Homolog of the Duchenne Locus Is Defective in X-Linked Muscular-Dystrophy of Dogs. Nature 1988; 334: 154-6.
43. Cordier L, Gao GP, Hack AA, et al. Muscle-specific promoters may be necessary for adeno-associated virus-mediated gene transfer in the treatment of muscular dystrophies. Hum Gene Ther 2001; 12: 205-15.
44. Corrado K, Rafael JA, Mills PL, et al. Transgenic mdx mice expressing dystrophin with a deletion in the actin-binding domain display a mild Becker phenotype. J Cell Biol 1996; 134: 873-84.
45. Cox GA, Sunada Y, Campbell KP. Chamberlain JS. Dp71 can restore the dystrophin-associated glycoprotein complex in muscle but fails to prevent dystrophy. Nat Genet 1994; 8: 333-9.
46. Crawford GE, Faulkner JA, Crosbie RH, et al. Assembly of the dystrophin-associated protein complex does not require the dystrophin COOH-terminal domain. J Cell Biol 2000; 150: 1399-410.
47. Davies KE, Pearson PL, Harper PS, et al. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. Nucleic Acids Res 1983; 11: 2303-12.
48. Deconinck AE, Rafael JA, Skinner JA, et al. Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 1997; 90: 717-27.
49. Di Pasquale G, Davidson BL, Stein CS, Martins IS, Scudiero D, Monks A, Chiorini JA. Identification of PDGFR as a receptor for AAV-5 transduction. Nat Med 2003; 9: 1306-12.
50. Dowling P, Culligan K, Ohlendieck K. Distal mdx muscle groups exhibiting up-regulation of utrophin and rescue of dystrophin-associated glycoproteins exemplify a protected phenotype in muscular dystrophy. Naturwissenschaften 2002; 89: 75-8.
51. Duan DS, Li Q, Kao AW, et al. Dynamin is required for recombinant adeno-associated virus type 2 infection. J Virol 1999; 73: 10371-6.
52. Duan DS, Sharma P, Yang JS, 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: 8568-77.
53. Dunckley MG, Love DR, Davies KE, et al. Retroviral-mediated transfer of a dystrophin minigene into mdx mouse myoblasts in vitro. FEBS Lett 1992; 296: 128-34.
54. Ebihara S, Guibinga GH, Gilbert R, et al. Differential effects of dystrophin and utrophin gene transfer in immunocompetent muscular dystrophy (mdx) mice. Physiol Genom 2000; 3: 133-44.
55. Fabbrizio E, Bonet-Kerrache A, Leger JJ, Mornet D. Actin-dystrophin interface. Biochemistry 1993; 32: 10457-63.
56. Fisher KJ, Jooss K, Alston J, et al. Recombinant adeno-associated virus for muscle directed gene therapy. Nat Med 1997; 3: 306-12.
57. Foster H, Sharp PS, Athanasopoulos T, et al. Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2/8 gene transfer. Mol Ther 2008; 16: 1825-32.
58. Fougerousse F, Bartoli M, Poupiot J, et al. Phenotypic correction of alpha-sarcoglycan deficiency by intra-arterial injection of a muscle-specific serotype 1 rAAV vector. Mol Ther: J Am Soc Gene Ther 2007; 15: 53-61.
59. Gao G, Vandenberghe LH, Alvira MR, et al. Clades of Adeno-associated viruses are widely disseminated in human tissues. J Virol 2004; 78: 6381-8.
60. Gao G, Wang Q, Calcedo R, et al. Adeno-associated virus-mediated gene transfer to nonhuman primate liver can elicit destructive transgene-specific T cell responses. Hum Gene Ther 2009; 20: 930-42.
61. Gao GP, Alvira MR, Wang L, et al. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA 2002; 99: 11854-9.
62. Gardner KL, Kearney JA, Edwards JD, Rafael-Fortney JA. Restoration of all dystrophin protein interactions by functional domains in trans does not rescue dystrophy. Gene Ther 2006; 13: 744-51.
63. Geisler A, Jungmann A, Kurreck J, et al. microRNA122-regulated transgene expression increases specificity of cardiac gene transfer upon intravenous delivery of AAV9 vectors. Gene Ther 2011; 18: 199-209.
64. Gentner B, Schira G, Giustacchini A, et al. Stable knockdown of microRNA in vivo by lentiviral vectors. Nat Meth 2009; 6: 63-6.
65. Ghosh A, Yue Y, Long C, Bostick B, Duan D. Efficient whole-body transduction with trans-splicing adeno-associated viral vectors. Mol Ther 2007; 15: 750-5.
66. Gilchrist SC, Ontell MP, Kochanek S, Clemens PR. Immune response to full-length dystrophin delivered to DMD muscle by a high-capacity adenoviral vector. Mol Ther 2002; 6: 359-68.
67. Goemans NM, Tulinius M, van den Akker JT, et al. Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med 2011; 364: 1513-22.
68. Goldberg LR, Hausmanowa-Petrusewicz I, Fidzianska A, et al. A dystrophin missense mutation showing persistence of dystrophin and dystrophin-associated proteins yet a severe phenotype. Ann Neurol 1998; 44: 971-6.
69. Grady RM, Grange RW, Lau KS, et al. Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies. Nat Cell Biol 1999; 1: 215-20.
70. Grady RM, Teng H, Nichol MC, et al. Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. Cell 1997; 90: 729-38.
71. Greenberg DS, Sunada Y, Campbell KP, Yaffe D, Nudel U. Exogenous Dp71 restores the levels of dystrophin associated proteins but does not alleviate muscle damage in mdx mice. Nat Genet 1994; 8: 340-4.
72. Gregorevic P, Allen JM, Minami E, et al. rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice. Nat Med 2006; 12: 787-9.
73. Gregorevic P, Blankinship MJ, Allen JM, et al. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med 2004; 10: 828-34.
74. Gregorevic P, Schultz BR, Allen JM, et al. Evaluation of vascular delivery methodologies to enhance rAAV6-mediated gene transfer to canine striated musculature. Mol Ther 2009; 17: 1427-33.
75. Grimm D, Kay MA. From virus evolution to vector revolution: use of naturally occurring serotypes of adeno-associated virus (AAV) as novel vectors for human gene therapy. Curr Gene Ther 2003; 3: 281-304.
76. Halbert CL, Standaert TA, Wilson CB, Miller AD. Successful readministration of adeno-associated virus vectors to the mouse lung requires transient immunosuppression during the initial exposure. J Virol 1998; 72: 9795-805.
77. Harper SQ, Hauser MA, DelloRusso C, et al. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med 2002; 8: 253-61.
78. Heemskerk H, de Winter CL, van Ommen GJ, van Deutekom JC, Aartsma-Rus A. Development of antisense-mediated exon skipping as a treatment for duchenne muscular dystrophy. Ann N Y Acad Sci 2009; 1175: 71-79.
79. Hemmings L, Kuhlman PA, Critchley DR. Analysis of the actin-binding domain of alpha-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain. J Cell Biol 1992; 116: 1369-80.
80. Herson S, Hentati F, Rigolet A, et al. A phase I trial of adeno-associated virus serotype 1-gamma-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C. Brain 2012; 135: 483-92.
81. Hoffman EP, Brown RH, Jr., Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987; 51: 919-28.
82. Huard J, Roy R, Bouchard J, et al. Human myoblast transplantation between immunohistocompatible donors and recipients produces immune reactions. Transplant Proc 1992; 24: 3049-51.
83. Im DS, Muzyczka N. The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell 1990; 61: 447-457.
84. Im WB, Phelps SF, Copen EH, et al. Differential expression of dystrophin isoforms in strains of mdx mice with different mutations. Hum Mol Genet 1996; 5: 1149-53.
85. Inagaki K, Fuess S, Storm TA, Gibson GA, et al. Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8. Mol Ther: J Am Soc Gene Ther 2006; 14: 45-53.
86. Ishikawa-Sakurai M, Yoshida M, Imamura M, Davies KE, Ozawa E. ZZ domain is essentially required for the physiological binding of dystrophin and utrophin to beta-dystroglycan. Hum Mol Genet 2004; 13: 693-702.
87. Jiang H, Couto LB, Patarroyo-White S, et al. Effects of transient immunosuppression on adeno-associated virus-mediated liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood 2006; 108: 3321-28.
88. Jooss K, Yang Y, Fisher KJ, Wilson JM. Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J Virol 1998; 72: 4212-23.
89. Kaludov N, Brown KE, Walters RW, Zabner J, Chiorini JA. 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 2001; 75: 6884-93.
90. Kashiwakura Y, Tamayose K, Iwabuchi K, et al. Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection. J Virol 2005; 79: 609-14.
91. 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 1996; 93: 14082-7.
92. Koenig M, Beggs AH, Moyer M, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 1989; 45: 498-506.
93. Koenig M, Hoffman EP, Bertelson CJ, et al. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 987; 50: 509-17.
94. Koenig M, Monaco AP, Kunkel LM. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 1988; 53: 219-28.
95. Koo T, Malerba A, Athanasopoulos T, et al. Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of alpha1-syntrophin and alpha-dystrobrevin in skeletal muscles of mdx mice. Hum Gene Ther 2011; 22: 1379-88.
96. Koo T, Okada T, Athanasopoulos T, et al. Long-term functional adeno-associated virus-microdystrophin expression in the dystrophic CXMDj dog. J Gene Med 2011; 13: 497-506.
97. 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: 1501-8.
98. Kotin RM. Large-scale recombinant adeno-associated virus production. Hum Mol Genet 2011; 20: R2-6.
99. Kotin RM, Menninger JC, Ward DC, Berns KI. Mapping and Direct Visualization of a Region-Specific Viral-DNA Integration Site on Chromosome-19q13-Qter. Genomics 1991; 10: 831-4.
100. Kunkel LM, Hejtmancik JF, Caskey CT, et al. Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 1986; 322: 73-7.
101. Kunkel LM, Monaco AP, Middlesworth W, Ochs HD, Latt SA. Specific cloning of DNA fragments absent from the DNA of a male patient with an X chromosome deletion. Proc Natl Acad Sci USA 1985; 82: 4778-82.
102. Lai Y, Thomas GD, Yue Y, et al. Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. J Clin Invest 2009; 119: 624-35.
103. Love DR, Hill DF, Dickson G, et al. An autosomal transcript in skeletal muscle with homology to dystrophin. Nature 1989; 339: 55-8.
104. Maheshri N, Koerber JT, Kaspar BK, Schaffer DV. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat Biotech 2006; 24: 198-204.
105. Manning WC, Zhou S, Bland MP, Escobedo JA, Dwarki V. Transient immunosuppression allows transgene expression following readministration of adeno-associated viral vectors. Hum Gene Ther 1998; 9: 477-85.
106. Manno CS: AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 2003; 101: 2963-72.
107. Manno CS, Arruda VR, Pierce GF, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 2006; 12: 342-7.
108. Matsumura K, Ervasti JM, Ohlendieck K, Kahl SD, Campbell KP. Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. Nature 1992; 360: 588-91.
109. Mays LE, Wilson JM. The complex and evolving story of T cell activation to AAV vector-encoded transgene products. Mol Ther 2011; 19: 16-27.
110. McCabe ER, Towbin J, Chamberlain J, et al. Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia. J Clin Invest 1989; 83: 95-9.
111. Mendell JR, Campbell K, Rodino-Klapac L, et al. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med 2010; 363: 1429-37.
112. Mendell JR, Rodino-Klapac LR, Rosales XQ, et al. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol 2010; 68: 629-38.
113. 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: 290-7.
114. Metzinger L, Blake DJ, Squier MV, et al. Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy. Hum Mol Genet 1997; 6: 1185-91.
115. Mingozzi F, High K. Immune responses to AAV in clinical trials. Current Gene Therapy 2007; 7: 316-24.
116. Mingozzi F, High K. Immune responses to AAV in clinical trials. Curr Gene Ther 2011; 11: 321-30.
117. Mingozzi F, Maus MV, Hui DJ, et al. CD8+ T-cell responses to adeno-associated virus capsid in humans. Nat Med 2007; 13: 419-22.
118. Mizuno Y, Nonaka I, Hirai S, Ozawa E. Reciprocal expression of dystrophin and utrophin in muscles of Duchenne muscular dystrophy patients, female DMD-carriers and control subjects. J Neurol Sci 1993; 119: 43-52.
119. 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: 2084-91.
120. Mori S, Wang L, Takeuchi T, Kanda T. Two novel adeno-associated viruses from cynomolgus monkey: pseudotyping characterization of capsid protein. Virology 2004; 330: 375-83.
121. Moskalenko M, Chen L, van Roey M, et al. Epitope mapping of human anti-adeno-associated virus type 2 neutralizing antibodies: implications for gene therapy and virus structure. J Virol 2000; 74: 1761-1766.
122. Nakai H, Fuess S, Storm TA, Muramatsu S, Nara Y, Kay MA. Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in mice. J Virol 2005; 79: 214-24.
123. Nakai H, Storm TA, Kay MA. Recruitment of single-stranded recombinant adeno-associated virus vector genomes and intermolecular recombination are responsible for stable transduction of liver in vivo. J Virol 2000; 74: 9451-63.
124. Odom GL, Gregorevic P, Allen JM, Chamberlain JS. Gene therapy of mdx mice with large truncated dystrophins generated by recombination using rAAV6. Mol Ther 2011; 19: 36-45.
125. Odom GL, Gregorevic P, Allen JM, Finn E, Chamberlain JS. Microutrophin delivery through rAAV6 increases lifespan and improves muscle function in dystrophic dystrophin/utrophin- deficient mice. Mol Ther 2008; 16: 1539-45.
126. Ohtsuka Y, Udaka K, Yamashiro Y, Yagita H, Okumura K. Dystrophin acts as a transplantation rejection antigen in dystrophin- deficient mice: implication for gene therapy. J Immunol 1998; 160: 4635-40.
127. 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: e3-9.
128. Palomeque J, Chemaly ER, Colosi P, et al. Efficiency of eight different AAV serotypes in transducing rat myocardium in vivo. Gene Ther 2007; 14: 989-97.
129. Pavalko FM, Otey CA. Role of adhesion molecule cytoplasmic domains in mediating interactions with the cytoskeleton. Proc Soc Exp Biol Med 1994; 205: 282-93.
130. Penaud-Budloo M, Le Guiner C, Nowrouzi A, et al. Adeno-associated virus vector genomes persist as episomal chromatin in primate muscle. J Virol 2008; 82: 7875-85.
131. Perabo L, Endell J, King S, et al. Combinatorial engineering of a gene therapy vector: directed evolution of adeno-associated virus. J Gene Med 2006; 8: 155-62.
132. Pfeifer A, Verma IM. Gene therapy: promises and problems. Ann Rev Genom Hum Genet 2001; 2: 177-211.
133. Phelps SF, Hauser MA, Cole NM, et al. Expression of full-length and truncated dystrophin mini-genes in transgenic mdx mice. Hum Mol Genet 1995; 4: 1251-8.
134. Phillips JL, Hegge J, Wolff JA, Samulski RJ, Asokan A. Systemic gene transfer to skeletal muscle using reengineered AAV vectors. Methods Mol Biol 2011; 709: 141-51.
135. Porter JD. Commentary: extraocular muscle sparing in muscular dystrophy: a critical evaluation of potential protective mechanisms. Neuromuscul Disord 1998; 8: 198-203.
136. Porter JD, Rafael JA, Ragusa RJ, et al. The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin. J Cell Sci 1998; 111 (Pt 13): 1801-11.
137. Prins KW, Humston JL, Mehta A, Tate V, Ralston E, Ervasti JM. Dystrophin is a microtubule-associated protein. J Cell Biol 2009; 186: 363-9.
138. Qiao C, Yuan Z, Li J, He B, Zheng H, Mayer C, Xiao X. Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver. Gene Ther 2011; 18: 403-10.
139. Qing K, Mah C, Hansen J, Zhou S, Dwarki V, Srivastava A. Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Nat Med 1999; 5: 71-7.
140. Rafael JA, Tinsley JM, Potter AC, Deconinck AE, Davies KE. Skeletal muscle-specific expression of a utrophin transgene rescues utrophin-dystrophin deficient mice. Nat Genet 1998; 19: 79-82.
141. Ray PN, Belfall B, Duff C, et al. Cloning of the breakpoint of an X;21 translocation associated with Duchenne muscular dystrophy. Nature 1985; 318: 672-5.
142. Reis e Sousa C, Hieny S, Scharton-Kersten T, et al. In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J Exp Med 1997; 186: 1819-29.
143. Rezniczek GA, Konieczny P, Nikolic B, et al. Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with beta-dystroglycan. J Cell Biol 2007; 176: 965-77.
144. Rivière C, Danos O, Douar AM. Long-term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice. Gene Ther 2006; 13: 1300-8.
145. 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: 109-17.
146. Rutledge EA, Halbert CL, Russell DW. Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. J Virol 1998; 72: 309-19.
147. Rybakova IN, Amann KJ, Ervasti JM. A new model for the interaction of dystrophin with F-actin. J Cell Biol 1996; 135: 661-72.
148. Sacco A, Mourkioti F, Tran R, et al. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell 2010; 143: 1059-71.
149. 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: 320-29.
150. Schatzberg SJ, Olby NJ, Breen M, et al. Molecular analysis of a spontaneous dystrophin 'knockout' dog. Neuromuscul Disord 1999; 9: 289-95.
151. Schmidt M, Voutetakis A, Afione S, et al. Adeno-associated virus type 12 (AAV12): a novel AAV serotype with sialic acid- and heparan sulfate proteoglycan-independent transduction activity. J Virol 2008; 82: 1399-406.
152. Schultz BR, Chamberlain JS. Recombinant adeno-associated virus transduction and integration. Mol Ther 2008; 16: 1189-99.
153. Seiler MP, Miller AD, Zabner J, Halbert CL. Adeno-associated virus types 5 and 6 use distinct receptors for cell entry. Hum Gene Ther 2006; 17: 10-19.
154. Seisenberger G, Ried MU, Endress T, et al. Real-time single-molecule imaging of the infection pathway of an adeno-associated virus. Science 2001; 294: 1929-32.
155. Shimatsu Y, Katagiri K, Furuta T, et al. Canine X-linked muscular dystrophy in Japan (CXMDJ). Exp Anim 2003; 52: 93-7.
156. Sicinski P, Geng Y, Ryder-Cook AS, et al. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 1989; 244: 1578-80.
157. Smith BF, Yue Y, Woods PR, et al. An intronic LINE-1 element insertion in the dystrophin gene aborts dystrophin expression and results in Duchenne-like muscular dystrophy in the corgi breed. Lab Invest 2011; 91: 216-31.
158. Smith RH, Kotin RM. The Rep52 gene product of adeno-associated virus is a DNA helicase with 3'-to-5' polarity. J Virol 1998; 72: 4874-81.
159. Snyder RO, Im DS, Ni T, et al. Features of the adeno-associated virus origin involved in substrate recognition by the viral Rep protein. J Virol 1993; 67: 6096-104.
160. Squire S, Raymackers JM, Vandebrouck C, et al. Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system. Hum Mol Genet 2002; 11: 3333-44.
161. Stone MR, O'Neill A, Catino D, Bloch RJ. Specific interaction of the actin-binding domain of dystrophin with intermediate filaments containing keratin 19. Mol Biol Cell 2005; 16: 4280-93.
162. Summerford C, Bartlett JS, Samulski RJ. AlphaVbeta5 integrin: a co-receptor for adeno-associated virus type 2 infection. Nat Med 1999; 5: 78-82.
163. Summerford C, Samulski RJ. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 1998; 72: 1438-45.
164. Tinsley J, Deconinck N, Fisher R, et al. Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat Med 1998; 4: 1441-4.
165. Tinsley JM, Blake DJ, Roche A, et al. Primary structure of dystrophin-related protein. Nature 1992; 360: 591-3.
166. Tinsley JM, Davies KE. Utrophin: a potential replacement for dystrophin? Neuromuscul Disord 1993; 3: 537-9.
167. Tinsley JM, Fairclough RJ, Storer R, et al. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS One 2011; 6: e19189.
168. Tinsley JM, Potter AC, Phelps SR, et al. Amelioration of the dystrophic phenotype of mdx mice using a truncated utrophin transgene. Nature 1996; 384: 349-53.
169. 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: 151-60.
170. Valentine BA, Cooper BJ, de Lahunta A, O'Quinn R, Blue JT. Canine X-linked muscular dystrophy. An animal model of Duchenne muscular dystrophy: clinical studies. J Neurol Sci 1988; 88: 69-81
171. van Deutekom JC, Janson AA, Ginjaar IB, et al. Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med 2007; 357: 2677-86.
172. Wakefield PM, Tinsley JM, Wood MJ, et al. Prevention of the dystrophic phenotype in dystrophin/utrophin-deficient muscle following adenovirus-mediated transfer of a utrophin minigene. Gene Ther 2000; 7: 201-4.
173. Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci USA 2000; 97: 13714-19.
174. Wang Z, Allen JM, Riddell SR, et al. Immunity to adeno-associated virus-mediated gene transfer in a random-bred canine model of Duchenne muscular dystrophy. Hum Gene Ther 2007; 18: 18-26.
175. Wang Z, Kuhr CS, Allen JM, et al. Sustained AAV-mediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression. Mol Ther 2007; 15: 1160-6.
176. Wang Z, Tapscott SJ, Chamberlain JS, Storb R. Immunity and AAV-Mediated Gene Therapy for Muscular Dystrophies in Large Animal Models and Human Trials. Front Microbiol 2011; 2: 201.
177. Wang Z, Zhu T, Qiao C, et al. Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nat Biotechnol 2005; 23: 321-8.
178. Warner LE, DelloRusso C, Crawford RW et al. Expression of Dp260 in muscle tethers the actin cytoskeleton to the dystrophinglycoprotein complex and partially prevents dystrophy. Hum Mol Genet 2002; 11: 1095-105.
179. Way M, Pope B, Cross RA, Kendrick-Jones J, Weeds AG. Expression of the N-terminal domain of dystrophin in E. coli and demonstration of binding to F-actin. FEBS Lett 1992; 301: 243-5.
180. Weir AP, Morgan JE, Davies KE. A-utrophin up-regulation in mdx skeletal muscle is independent of regeneration. Neuromuscular Disord 2004; 14: 19-23.
181. Weller ML, Amornphimoltham P, Schmidt M, et al. Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6. Nat Med 2010; 16: 662-4.
182. Wells DJ, Ferrer A and Wells KE. Immunological hurdles in the path to gene therapy for Duchenne muscular dystrophy. Expert Rev Mol Med 2002; 4: 1-23.
183. Wells DJ, Wells KE, Asante EA, et al. Expression of human fulllength and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy. Hum Mol Genet 1995; 4: 1245-50.
184. Winder SJ: The membrane-cytoskeleton interface: the role of dystrophin and utrophin. J Muscle Res Cell Motil 1997; 18: 617-629.
185. Winder SJ, Hemmings L, Maciver SK, et al. Utrophin actin binding domain: analysis of actin binding and cellular targeting. J Cell Sci 1995; 108: 63-71.
186. Wu ZJ, Miller E, Agbandje-McKenna M, Samulski RJ. alpha 2,3 and alpha 2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6. J Virol 2006; 80: 9093-103.
187. Xiao W, Chirmule N, Berta SC, et al. Gene therapy vectors based on adeno-associated virus type 1. J Virol 1999; 73: 3994-4003.
188. Xiao X, Li J and Samulski RJ. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol 1996; 70: 8098-108.
189. Xie Q, Bu W, Bhatia S, et al. The atomic structure of adenoassociated virus (AAV-2), a vector for human gene therapy. Proc Natl Acad Sci USA 2002; 99: 10405-10.
190. Yang JS, Zhou WH, Zhang YL, et al. Concatamerization of adenoassociated virus circular genomes occurs through intermolecular recombination. J Virol 1999; 73: 9468-77.
191. Yuasa K, Sakamoto M, Miyagoe-Suzuki Y, et al. Adeno-associated virus vector-mediated gene transfer into dystrophin-deficient skeletal muscles evokes enhanced immune response against the transgene product. Gene Ther 2002; 9: 1576-88.
192. 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: 1944-52.
193. Zaiss A-K, Liu Q, Bowen GP, et al. Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. J Virol 2002; 76: 4580-90.
194. Zincarelli C, Soltys S, Rengo G, Koch WJ, Rabinowitz JE. Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart. Clin Transl Sci 2010; 3: 81-9.
195. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther 2008; 16: 1073-80.