The AAV vector toolkit: Poised at the clinical crossroads

Molecular Therapy

Volumn 20, Issue 4, 2012, Pages 699-708

  Asokan, Aravind ^a   Schaffer, David V ^b,c   Samulski, R Jude ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b University of California   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PARVOVIRUS VECTOR;

CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM; CLINICAL PRACTICE; CLINICAL STUDY; DOSE RESPONSE; EXPERIMENTAL ANIMAL; GENE THERAPY; GENE TRANSFER; GENETIC DISORDER; GENETIC ENGINEERING; HUMAN; HUMORAL IMMUNITY; LIVER; MOLECULAR GENETICS; MUSCULOSKELETAL SYSTEM; NONHUMAN; PARVOVIRUS; PROTEIN EXPRESSION; RESPIRATORY SYSTEM; RETINA; REVIEW; SEROTYPE; SPECIES DIFFERENCE; TROPISM; VIRUS ISOLATION; VIRUS STRAIN; VISUAL SYSTEM;

ADENO-ASSOCIATED VIRUS; ANIMALIA; MIRIDAE;

EID: 84859440283     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2011.287     Document Type: Review

References (141)

1. Bowles, DE, Rabinowitz, JE and Samulski, RJ (2006). The genus Dependovirus. In: Kerr JR, Cotmore SF, Bloom ME, Linden RM and Parrish CR (eds). Parvoviruses. Hodder Arnold Education: London, UK. pp.15-24.
2. Mingozzi, F and High, KA (2011). Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet 12: 341-355.
3. Maguire, AM, Simonelli, F, Pierce, EA, Pugh, EN Jr, Mingozzi, F, Bennicelli, J et al. (2008). Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med 358: 2240-2248. (Pubitemid 351724453)
4. Maguire, AM, High, KA, Auricchio, A, Wright, JF, Pierce, EA, Testa, F et al. (2009). Agedependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet 374: 1597-1605.
5. Bainbridge, JW, Smith, AJ, Barker, SS, Robbie, S, Henderson, R, Balaggan, K et al. (2008). Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med 358: 2231-2239. (Pubitemid 351724452)
6. Hauswirth, WW, Aleman, TS, Kaushal, S, Cideciyan, AV, Schwartz, SB, Wang, L et al. (2008). Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther 19: 979-990.
7. Cideciyan, AV, Aleman, TS, Boye, SL, Schwartz, SB, Kaushal, S, Roman, AJ et al. (2008). Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci USA 105: 15112-15117.
8. Cideciyan, AV, Hauswirth, WW, Aleman, TS, Kaushal, S, Schwartz, SB, Boye, SL et al. (2009). Vision 1 year after gene therapy for Leber's congenital amaurosis. N Engl J Med 361: 725-727.
9. Simonelli, F, Maguire, AM, Testa, F, Pierce, EA, Mingozzi, F, Bennicelli, JL et al. (2010). Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther 18: 643-650.
10. Gao, G, Vandenberghe, LH and Wilson, JM (2005). New recombinant serotypes of AAV vectors. Curr Gene Ther 5: 285-297. (Pubitemid 40895013)
11. Xiao, W, Chirmule, N, Berta, SC, McCullough, B, Gao, G and Wilson, JM (1999). Gene therapy vectors based on adeno-associated virus type 1. J Virol 73: 3994-4003. (Pubitemid 29189844)
12. Chiorini, JA, Yang, L, Liu, Y, Safer, B and Kotin, RM (1997). Cloning of adenoassociated virus type 4 (AAV4) and generation of recombinant AAV4 particles. J Virol 71: 6823-6833. (Pubitemid 27355343)
13. Rutledge, EA, Halbert, CL and Russell, DW (1998). Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. J Virol 72: 309-319. (Pubitemid 28048842)
14. Hurlbut, GD, Ziegler, RJ, Nietupski, JB, Foley, JW, Woodworth, LA, Meyers, E et al. (2010). Preexisting immunity and low expression in primates highlight translational challenges for liver-directed AAV8-mediated gene therapy. Mol Ther 18: 1983-1994.
15. Bell, P, Gao, G, Haskins, ME, Wang, L, Sleeper, MM, Wang, H et al. (2011). Evaluation of AAV vectors for liver-directed gene transfer in dogs. Hum. Gene Ther 2: 985-997.
16. Nathwani, AC, Gray, JT, Ng, CY, Zhou, J, Spence, Y, Waddington, SN et al. (2006). Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood 107: 2653-2661.
17. Nathwani, AC, Gray, JT, McIntosh, J, Ng, CY, Zhou, J, Spence, Y et al. (2007). Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood 109: 1414-1421. (Pubitemid 46239572)
18. Gao, GP, Lu, Y, Sun, X, Johnston, J, Calcedo, R, Grant, R et al. (2006). High-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomes. J Virol 80: 6192-6194. (Pubitemid 43849199)
19. Wang, L, Calcedo, R, Nichols, TC, Bellinger, DA, Dillow, A, Verma, IM et al. (2005). Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy. Blood 105: 3079-3086.
20. Jiang, H, Couto, LB, Patarroyo-White, S, Liu, T, Nagy, D, Vargas, JA et al. (2006). Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood 108: 3321-3328.
21. Sarkar, R, Mucci, M, Addya, S, Tetreault, R, Bellinger, DA, Nichols, TC et al. (2006). Long-term efficacy of adeno-associated virus serotypes 8 and 9 in hemophilia a dogs and mice. Hum Gene Ther 17: 427-439.
22. Monahan, PE, Lothrop, CD, Sun, J, Hirsch, ML, Kafri, T, Kantor, B et al. (2010). Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large genomes in hemophilia mouse and dog models: a strategy for broad clinical application. Mol Ther 18: 1907-1916.
23. Mattar, CN, Nathwani, AC, Waddington, SN, Dighe, N, Kaeppel, C, Nowrouzi, A et al. (2011). Stable human FIX expression after 0.9G intrauterine gene transfer of self-complementary adeno-associated viral vector 5 and 8 in macaques. Mol Ther 19: 1950-1960.
24. Wang, L, Bell, P, Lin, J, Calcedo, R, Tarantal, AF and Wilson, JM (2011). AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta). Mol Ther 19: 2012-2020.
25. Nathwani, A, Tuddenham, E, Rosales, C, McIntosh, J, Riddell, A, Rustagi, P et al. (2010). Early Clinical Trial Results Following Administration of a Low Dose of a Novel Self Complementary Adeno-Associated Viral Vector Encoding Human Factor IX In Two Subjects with Severe Hemophilia B. ASH Annual Meeting Abstracts 116: 248.
26. Wang, L, Calcedo, R, Wang, H, Bell, P, Grant, R, Vandenberghe, LH et al. (2010). The pleiotropic effects of natural AAV infections on liver-directed gene transfer in macaques. Mol Ther 18: 126-134.
27. Wang, L, Calcedo, R, Bell, P, Lin, J, Grant, RL, Siegel, DL et al. (2011). Impact of Pre-Existing Immunity on Gene Transfer to Nonhuman Primate Liver with Adeno-Associated Virus 8 Vectors. Hum Gene Ther 22: 1389-1401.
28. Li, C, Narkbunnam, N, Samulski, RJ, Asokan, A, Hu, G, Jacobson, LJ et al. (2011). Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia. Gene Ther (epub ahead of print).
29. Boutin, S, Monteilhet, V, Veron, P, Leborgne, C, Benveniste, O, Montus, MF et al. (2010). 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 21: 704-712.
30. Calcedo, R, Vandenberghe, LH, Gao, G, Lin, J and Wilson, JM (2009). Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis 199: 381-390.
31. Wang, Q, Gurda, B, Vandenberghe, L, Lu, J, Li, S and Wilson, JM (2011). Selection of neutralizing antibody-resistant AAV8 variants with structure-guided site-specific saturated mutagenesis. Mol Ther 19: S129.
32. Nam, HJ, Lane, MD, Padron, E, Gurda, B, McKenna, R, Kohlbrenner, E et al. (2007). Structure of adeno-associated virus serotype 8, a gene therapy vector. J Virol 81: 12260-12271. (Pubitemid 350085841)
33. Kawase, Y, Ly, HQ, Prunier, F, Lebeche, D, Shi, Y, Jin, H et al. (2008). Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure. J Am Coll Cardiol 51: 1112-1119. (Pubitemid 351374774)
34. Hadri, L, Bobe, R, Kawase, Y, Ladage, D, Ishikawa, K, Atassi, F et al. (2010). SERCA2a gene transfer enhances eNOS expression and activity in endothelial cells. Mol Ther 18: 1284-1292.
35. Hajjar, RJ, Zsebo, K, Deckelbaum, L, Thompson, C, Rudy, J, Yaroshinsky, A et al. (2008). Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail 14: 355-367. (Pubitemid 351756538)
36. Qiao, C, Li, J, Zheng, H, Bogan, J, Li, J, Yuan, Z et al. (2009). 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 20: 1-10.
37. Toromanoff, A, Adjali, O, Larcher, T, Hill, M, Guigand, L, Chenuaud, P et al. (2010). Lack of immunotoxicity after regional intravenous (RI) delivery of rAAV to nonhuman primate skeletal muscle. Mol Ther 18: 151-160.
38. Toromanoff, A, Chérel, Y, Guilbaud, M, Penaud-Budloo, M, Snyder, RO, Haskins, ME et al. (2008). Safety and efficacy of regional intravenous (r.i.) versus intramuscular (i.m.) delivery of rAAV1 and rAAV8 to nonhuman primate skeletal muscle. Mol Ther 16: 1291-1299. (Pubitemid 351866061)
39. Raake, PW, Hinkel, R, Müller, S, Delker, S, Kreuzpointner, R, Kupatt, C et al. (2008). Cardio-specific long-term gene expression in a porcine model after selective pressureregulated retroinfusion of adeno-associated viral (AAV) vectors. Gene Ther 15: 12-17. (Pubitemid 350284205)
40. Bish, LT, Sleeper, MM, Reynolds, C, Gazzara, J, Withnall, E, Singletary, GE et al. (2011). Cardiac gene transfer of short hairpin RNA directed against phospholamban effectively knocks down gene expression but causes cellular toxicity in canines. Hum Gene Ther 22: 969-977.
41. White, JD, Thesier, DM, Swain, JB, Katz, MG, Tomasulo, C, Henderson, A et al. (2011). Myocardial gene delivery using molecular cardiac surgery with recombinant adenoassociated virus vectors in vivo. Gene Ther 18: 546-552.
42. Kota, J, Handy, CR, Haidet, AM, Montgomery, CL, Eagle, A, Rodino-Klapac, LR et al. (2009). Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med 1: 6ra15.
43. Wang, Z, Kuhr, CS, Allen, JM, Blankinship, M, Gregorevic, P, Chamberlain, JS et al. (2007). Sustained AAV-mediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression. Mol Ther 15: 1160-1166. (Pubitemid 46813619)
44. Brantly, ML, Chulay, JD, Wang, L, Mueller, C, Humphries, M, Spencer, LT et al. (2009). Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci USA 106: 16363-16368.
45. Flotte, TR, Trapnell, BC, Humphries, M, Carey, B, Calcedo, R, Rouhani, F et al. (2011). Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing alpha(1)-antitrypsin: interim results. Hum Gene Ther 22: 1239-1247.
46. Stroes, ES, Nierman, MC, Meulenberg, JJ, Franssen, R, Twisk, J, Henny, CP et al. (2008). Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol 28: 2303-2304.
47. Pacak, CA, Mah, CS, Thattaliyath, BD, Conlon, TJ, Lewis, MA, Cloutier, DE et al. (2006). Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ Res 99: e3-e9. (Pubitemid 44255502)
48. Pleger, ST, Shan, C, Ksienzyk, J, Bekeredjian, R, Boekstegers, P, Hinkel, R et al. (2011). Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model. Sci Transl Med 3: 92ra64.
49. Gao, G, Bish, LT, Sleeper, MM, Mu, X, Sun, L, Lou, Y et al. (2011). Transendocardial delivery of AAV6 results in highly efficient and global cardiac gene transfer in rhesus macaques. Hum Gene Ther 22: 979-984.
50. Kornegay, JN, Li, J, Bogan, JR, Bogan, DJ, Chen, C, Zheng, H et al. (2010). Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs. Mol Ther 18: 1501-1508.
51. Hadaczek, P, Kohutnicka, M, Krauze, MT, Bringas, J, Pivirotto, P, Cunningham, J et al. (2006). Convection-enhanced delivery of adeno-associated virus type 2 (AAV2) into the striatum and transport of AAV2 within monkey brain. Hum Gene Ther 17: 291-302.
52. Kells, AP, Hadaczek, P, Yin, D, Bringas, J, Varenika, V, Forsayeth, J et al. (2009). Efficient gene therapy-based method for the delivery of therapeutics to primate cortex. Proc Natl Acad Sci USA 106: 2407-2411.
53. Bankiewicz, KS, Forsayeth, J, Eberling, JL, Sanchez-Pernaute, R, Pivirotto, P, Bringas, J et al. (2006). Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther 14: 564-570. (Pubitemid 44296090)
54. Forsayeth, JR, Eberling, JL, Sanftner, LM, Zhen, Z, Pivirotto, P, Bringas, J et al. (2006). A dose-ranging study of AAV-hAADC therapy in Parkinsonian monkeys. Mol Ther 14: 571-577. (Pubitemid 44296089)
55. Hadaczek, P, Eberling, JL, Pivirotto, P, Bringas, J, Forsayeth, J and Bankiewicz, KS (2010). Eight years of clinical improvement in MPTP-lesioned primates after gene therapy with AAV2-hAADC. Mol Ther 18: 1458-1461.
56. Hadaczek, P, Forsayeth, J, Mirek, H, Munson, K, Bringas, J, Pivirotto, P et al. (2009). Transduction of nonhuman primate brain with adeno-associated virus serotype 1: vector trafficking and immune response. Hum Gene Ther 20: 225-237.
57. Dodiya, HB, Bjorklund, T, Stansell, J 3rd, Mandel, RJ, Kirik, D and Kordower, JH (2010). Differential transduction following basal ganglia administration of distinct pseudotyped AAV capsid serotypes in nonhuman primates. Mol Ther 18: 579-587.
58. Colle, MA, Piguet, F, Bertrand, L, Raoul, S, Bieche, I, Dubreil, L et al. (2010). Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate. Hum Mol Genet 19: 147-158.
59. Markakis, EA, Vives, KP, Bober, J, Leichtle, S, Leranth, C, Beecham, J et al. (2010). Comparative transduction efficiency of AAV vector serotypes 1-6 in the substantia nigra and striatum of the primate brain. Mol Ther 18: 588-593.
60. Gao, G, Vandenberghe, LH, Alvira, MR, Lu, Y, Calcedo, R, Zhou, X et al. (2004). Clades of Adeno-associated viruses are widely disseminated in human tissues. J Virol 78: 6381-6388. (Pubitemid 38715936)
61. Cearley, CN and Wolfe, JH (2006). Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain. Mol Ther 13: 528-537. (Pubitemid 43257620)
62. Sondhi, D, Hackett, NR, Peterson, DA, Stratton, J, Baad, M, Travis, KM et al. (2007). Enhanced survival of the LINCL mouse following CLN2 gene transfer using the rh.10 rhesus macaque-derived adeno-associated virus vector. Mol Ther 15: 481-491.
63. Foust, KD, Nurre, E, Montgomery, CL, Hernandez, A, Chan, CM and Kaspar, BK (2009). Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 27: 59-65.
64. Gray, SJ, Matagne, V, Bachaboina, L, Yadav, S, Ojeda, SR and Samulski, RJ (2011). Preclinical Differences of Intravascular AAV9 Delivery to Neurons and Glia: A Comparative Study of Adult Mice and Nonhuman Primates. Mol Ther 19: 1058-1069.
65. Bevan, AK, Duque, S, Foust, KD, Morales, PR, Braun, L, Schmelzer, L et al. (2011). Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. Mol Ther 19: 1971-1980.
66. Zhang, H, Yang, B, Mu, X, Ahmed, SS, Su, Q, He, R et al. (2011). Several rAAV vectors efficiently cross the blood-brain barrier and transduce neurons and astrocytes in the neonatal mouse central nervous system. Mol Ther 19: 1440-1448.
67. Acland, GM, Aguirre, GD, Bennett, J, Aleman, TS, Cideciyan, AV, Bennicelli, J et al. (2005). Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther 12: 1072-1082. (Pubitemid 41723041)
68. Le Meur, G, Stieger, K, Smith, AJ, Weber, M, Deschamps, JY, Nivard, D et al. (2007). Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. Gene Ther 14: 292-303. (Pubitemid 46231923)
69. Stieger, K, Colle, MA, Dubreil, L, Mendes-Madeira, A, Weber, M, Le Meur, G et al. (2008). Subretinal delivery of recombinant AAV serotype 8 vector in dogs results in gene transfer to neurons in the brain. Mol Ther 16: 916-923. (Pubitemid 351587102)
70. Vandenberghe, LH, Bell, P, Maguire, AM, Cearley, CN, Xiao, R, Calcedo, R et al. (2011). Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey. Sci Transl Med 3: 88ra54.
71. Moss, RB, Milla, C, Colombo, J, Accurso, F, Zeitlin, PL, Clancy, JP et al. (2007). Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: a randomized placebocontrolled phase 2B trial. Hum Gene Ther 18: 726-732. (Pubitemid 47378069)
72. Flotte, TR, Fischer, AC, Goetzmann, J, Mueller, C, Cebotaru, L, Yan, Z et al. (2010). Dual reporter comparative indexing of rAAV pseudotyped vectors in chimpanzee airway. Mol Ther 18: 594-600.
73. Halbert, CL, Madtes, DK, Vaughan, AE, Wang, Z, Storb, R, Tapscott, SJ et al. (2010). Expression of human alpha1-antitrypsin in mice and dogs following AAV6 vectormediated gene transfer to the lungs. Mol Ther 18: 1165-1172.
74. Sun, X, Sui, H, Fisher, JT, Yan, Z, Liu, X, Cho, HJ et al. (2010). Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis. J Clin Invest 120: 3149-3160.
75. Stoltz, DA, Meyerholz, DK, Pezzulo, AA, Ramachandran, S, Rogan, MP, Davis, GJ et al. (2010). Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2: 29ra31.
76. Ostedgaard LS, Meyerholz DK, Chen JH, Pezzulo AA, Karp PH, Rokhlina T et al. (2011). The DeltaF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs. Sci Transl Med 3: 74ra24.
77. Schmidt, M and Chiorini, JA (2006). Gangliosides are essential for bovine adenoassociated virus entry. J Virol 80: 5516-5522.
78. Schmidt, M, Govindasamy, L, Afione, S, Kaludov, N, Agbandje-McKenna, M and Chiorini, JA (2008). Molecular characterization of the heparin-dependent transduction domain on the capsid of a novel adeno-associated virus isolate, AAV(VR-942). J Virol 82: 8911-8916.
79. Schmidt, M, Voutetakis, A, Afione, S, Zheng, C, Mandikian, D and Chiorini, JA (2008). Adeno-associated virus type 12 (AAV12): a novel AAV serotype with sialic acid-and heparan sulfate proteoglycan-independent transduction activity. J Virol 82: 1399-1406.
80. De, BP, Heguy, A, Hackett, NR, Ferris, B, Leopold, PL, Lee, J et al. (2006). High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. Mol Ther 13: 67-76. (Pubitemid 41763484)
81. Watanabe, M, Boyer, JL and Crystal, RG (2010). AAVrh.10-mediated genetic delivery of bevacizumab to the pleura to provide local anti-VEGF to suppress growth of metastatic lung tumors. Gene Ther 17: 1042-1051.
82. Smith, LJ, Van Vliet, K, Miller, E, Kauss, MA, Ul-Hasan, TB, Wong, KK et al. (2011). Functional mapping of tissue tropism of naturally occurring adeno-associated virus isolates from human hematopoietic stem cells. Mol Ther 19: S127-S128.
83. Zhong, L, Li, M, Xie, J, Su, Q, He, R, Zhang, Y et al. (2011). Characterization of chimpanzee-derived novel natural variants of AAV5. Mol Ther 19: S155.
84. Zhong, L, Li, B, Mah, CS, Govindasamy, L, Agbandje-McKenna, M, Cooper, M et al. (2008). 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 105: 7827-7832. (Pubitemid 351872723)
85. Cheng B, Ling C, Dai Y, Lu Y, Glushakova LG, Gee SW et al. (2011). Development of optimized AAV3 serotype vectors: mechanism of high-efficiency transduction of human liver cancer cells. Gene Ther (epub ahead of print).
86. Qiao, C, Zhang, W, Yuan, Z, Shin, JH, Li, J, Jayandharan, GR et al. (2010). Adenoassociated virus serotype 6 capsid tyrosine-to-phenylalanine mutations improve gene transfer to skeletal muscle. Hum Gene Ther 21: 1343-1348.
87. Petrs-Silva, H, Dinculescu, A, Li, Q, Min, SH, Chiodo, V, Pang, JJ et al. (2009). Highefficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol Ther 17: 463-471.
88. Petrs-Silva, H, Dinculescu, A, Li, Q, Deng, WT, Pang, JJ, Min, SH et al. (2011). Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Mol Ther 19: 293-301.
89. Pang, JJ, Dai, X, Boye, SE, Barone, I, Boye, SL, Mao, S et al. (2011). Long-term retinal function and structure rescue using capsid mutant AAV8 vector in the rd10 mouse, a model of recessive retinitis pigmentosa. Mol Ther 19: 234-242.
90. Aslanidi, GV, Govindasamy, L, Ling, C, Zolotukhin, S, Agbandje-McKenna, M and Srivastava, A (2011). Site-directed mutagenesis of a surface-exposed serine residue leads to high-efficiency transduction by recombinant adeno-associated virus 2 vectors. Mol Ther 19: S128.
91. Bowles, DE, McPhee, SW, Li, C, Gray, SJ, Samulski, JJ, Camp, AS et al. (2011). Phase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV Vector. Mol Ther (epub ahead of print).
92. Mendell, JR, Campbell, K, Rodino-Klapac, L, Sahenk, Z, Shilling, C, Lewis, S et al. (2010). Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med 363: 1429-1437.
93. Vandenberghe, LH, Breous, E, Nam, HJ, Gao, G, Xiao, R, Sandhu, A et al. (2009). Naturally occurring singleton residues in AAV capsid impact vector performance and illustrate structural constraints. Gene Ther 16: 1416-1428.
94. Limberis, MP, Vandenberghe, LH, Zhang, L, Pickles, RJ and Wilson, JM (2009). Transduction efficiencies of novel AAV vectors in mouse airway epithelium in vivo and human ciliated airway epithelium in vitro. Mol Ther 17: 294-301.
95. Song, Y, Lou, HH, Boyer, JL, Limberis, MP, Vandenberghe, LH, Hackett, NR et al. (2009). Functional cystic fibrosis transmembrane conductance regulator expression in cystic fibrosis airway epithelial cells by AAV6.2-mediated segmental trans-splicing. Hum Gene Ther 20: 267-281.
96. Asokan, A, Conway, JC, Phillips, JL, Li, C, Hegge, J, Sinnott, R et al. (2010). Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Nat Biotechnol 28: 79-82.
97. Kern, A, Schmidt, K, Leder, C, Müller, OJ, Wobus, CE, Bettinger, K et al. (2003). Identification of a heparin-binding motif on adeno-associated virus type 2 capsids. J Virol 77: 11072-11081. (Pubitemid 37204297)
98. Asokan, A, Hegge, J, Grieger, JC, Li, C, Yadav, S, Samulski, JJ et al. (2010). Validation of intravascular administration of adeno-associated virus for muscular dystrophies in a non-human primate model. Mol. Ther. 18: S61-S62.
99. Fan, Z, Kocis, K, Valley, R, Howard, JF, Chopra, M, An, H et al. (2011). Safety and Feasibility of High-pressure Transvenous Limb Perfusion With 0.9% Saline in Human Muscular Dystrophy. Mol Ther (epub ahead of print).
100. Mays, LE, Vandenberghe, LH, Xiao, R, Bell, P, Nam, HJ, Agbandje-McKenna, M et al. (2009). Adeno-associated virus capsid structure drives CD4-dependent CD8+ T cell response to vector encoded proteins. J Immunol 182: 6051-6060.
101. Lin, SW, Hensley, SE, Tatsis, N, Lasaro, MO and Ertl, HC (2007). Recombinant adenoassociated virus vectors induce functionally impaired transgene product-specific CD8+ T cells in mice. J Clin Invest 117: 3958-3970. (Pubitemid 350224105)
102. Müller, OJ, Kaul, F, Weitzman, MD, Pasqualini, R, Arap, W, Kleinschmidt, JA et al. (2003). Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nat Biotechnol 21: 1040-1046. (Pubitemid 37064733)
103. Michelfelder, S and Trepel, M (2009). Adeno-associated viral vectors and their redirection to cell-type specific receptors. Adv Genet 67: 29-60.
104. Chen, YH, Chang, M and Davidson, BL (2009). Molecular signatures of disease brain endothelia provide new sites for CNS-directed enzyme therapy. Nat Med 15: 1215-1218.
105. Koerber, JT, Klimczak, R, Jang, JH, Dalkara, D, Flannery, JG and Schaffer, DV (2009). Molecular evolution of adeno-associated virus for enhanced glial gene delivery. Mol Ther 17: 2088-2095.
106. Jang, JH, Koerber, JT, Kim, JS, Asuri, P, Vazin, T, Bartel, M et al. (2011). An evolved adeno-associated viral variant enhances gene delivery and gene targeting in neural stem cells. Mol Ther 19: 667-675.
107. Rapti, K, Louis-Jeune, V, Kohlbrenner, E, Ishikawa, K, Ladage, D, Zolotukhin, S et al. (2011). Neutralizing Antibodies Against AAV Serotypes 1, 2, 6, and 9 in Sera of Commonly Used Animal Models. Mol Ther (epub ahead of print).
108. Maheshri, N, Koerber, JT, Kaspar, BK and Schaffer, DV (2006). Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat Biotechnol 24: 198-204. (Pubitemid 43221704)
109. Maersch, S, Huber, A, Büning, H, Hallek, M and Perabo, L (2010). Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes. Virology 397: 167-175.
110. Excoffon, KJ, Koerber, JT, Dickey, DD, Murtha, M, Keshavjee, S, Kaspar, BK et al. (2009). Directed evolution of adeno-associated virus to an infectious respiratory virus. Proc Natl Acad Sci USA 106: 3865-3870.
111. Li, W, Zhang, L, Johnson, JS, Zhijian, W, Grieger, JC, Ping-Jie, X et al. (2009). Generation of novel AAV variants by directed evolution for improved CFTR delivery to human ciliated airway epithelium. Mol Ther 17: 2067-2077.
112. Yang, L, Jiang, J, Drouin, LM, Agbandje-McKenna, M, Chen, C, Qiao, C et al. (2009). A myocardium tropic adeno-associated virus (AAV) evolved by DNA shuffling and in vivo selection. Proc Natl Acad Sci USA 106: 3946-3951.
113. Pulicherla, N, Shen, S, Yadav, S, Debbink, K, Govindasamy, L, Agbandje-McKenna, M et al. (2011). Engineering Liver-detargeted AAV9 Vectors for Cardiac and Musculoskeletal Gene Transfer. Mol Ther 19: 1070-1078.
114. Dalkara, D, Kolstad, KD, Guerin, KI, Hoffmann, NV, Visel, M, Klimczak, RR et al. (2011). AAV mediated GDNF secretion from retinal glia slows down retinal degeneration in a rat model of retinitis pigmentosa. Mol Ther 19: 1602-1608.
115. Maguire, CA, Gianni, D, Meijer, DH, Shaket, LA, Wakimoto, H, Rabkin, SD et al. (2010). Directed evolution of adeno-associated virus for glioma cell transduction. J Neurooncol 96: 337-347.
116. Gray, SJ, Blake, BL, Criswell, HE, Nicolson, SC, Samulski, RJ, McCown, TJ et al. (2010). Directed evolution of a novel adeno-associated virus (AAV) vector that crosses the seizure-compromised blood-brain barrier (BBB). Mol Ther 18: 570-578.
117. Dickey, DD, Bergen, J, Nassar, B, Steines, B, Excoffon, KJ, Schaffer, DV et al. (2011). Directed evolution of AAV in pig airway epithelia in vivo. Mol Ther 19: S251.
118. Lisowski, L, Chu, K and Kay, MA (2011). Shuffled AAV library selection on human hepatocytes in vivo. Mol Ther 19: S128-S129.
119. Wu, Z, Miller, E, Agbandje-McKenna, M and Samulski, RJ (2006). Alpha2,3 and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adenoassociated virus types 1 and 6. J Virol 80: 9093-9103. (Pubitemid 44359983)
120. Weller, ML, Amornphimoltham, P, Schmidt, M, Wilson, PA, Gutkind, JS and Chiorini, JA (2010). Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6. Nat Med 16: 662-664.
121. Ng, R, Govindasamy, L, Gurda, BL, McKenna, R, Kozyreva, OG, Samulski, RJ et al. (2010). Structural characterization of the dual glycan binding adeno-associated virus serotype 6. J Virol 84: 12945-12957.
122. Summerford, C and Samulski, RJ (1998). Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 72: 1438-1445. (Pubitemid 28116931)
123. Qing, K, Mah, C, Hansen, J, Zhou, S, Dwarki, V and Srivastava, A (1999). Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Nat Med 5: 71-77. (Pubitemid 29051001)
124. Akache, B, Grimm, D, Pandey, K, Yant, SR, Xu, H and Kay, MA (2006). The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9. J Virol 80: 9831-9836. (Pubitemid 44435657)
125. Kashiwakura, Y, Tamayose, K, Iwabuchi, K, Hirai, Y, Shimada, T, Matsumoto, K et al. (2005). Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection. J Virol 79: 609-614. (Pubitemid 39648414)
126. Summerford, C, Bartlett, JS and Samulski, RJ (1999). AlphaVbeta5 integrin: a co-receptor for adeno-associated virus type 2 infection. Nat Med 5: 78-82. (Pubitemid 29051002)
127. Asokan, A, Hamra, JB, Govindasamy, L, Agbandje-McKenna, M and Samulski, RJ (2006). Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry. J Virol 80: 8961-8969. (Pubitemid 44359970)
128. Xie, Q, Bu, W, Bhatia, S, Hare, J, Somasundaram, T, Azzi, A et al. (2002). The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Proc Natl Acad Sci USA 99: 10405-10410.
129. Gao, GP, Alvira, MR, Wang, L, Calcedo, R, Johnston, J and Wilson, JM (2002). Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA 99: 11854-11859. (Pubitemid 34994488)
130. Nam, HJ, Lane, MD, Padron, E, Gurda, B, McKenna, R, Kohlbrenner, E et al. (2007). Structure of adeno-associated virus serotype 8, a gene therapy vector. J. Virol. 81: 12260-12271. (Pubitemid 350085841)
131. Mori, S, Wang, L, Takeuchi, T and Kanda, T (2004). Two novel adeno-associated viruses from cynomolgus monkey: pseudotyping characterization of capsid protein. Virology 330: 375-383. (Pubitemid 39572844)
132. Shen, S, Bryant, KD, Brown, SM, Randell, SH and Asokan, A (2011). Terminal N-linked galactose is the primary receptor for adeno-associated virus 9. J Biol Chem 286: 13532-13540.
133. Lerch, TF, Xie, Q and Chapman, MS (2010). The structure of adeno-associated virus serotype 3B (AAV-3B): insights into receptor binding and immune evasion. Virology 403: 26-36.
134. Ling, C, Lu, Y, Kalsi, JK, Jayandharan, GR, Li, B, Ma, W et al. (2010). Human hepatocyte growth factor receptor is a cellular coreceptor for adeno-associated virus serotype 3. Hum Gene Ther 21: 1741-1747.
135. Kaludov, N, Brown, KE, Walters, RW, Zabner, J and Chiorini, JA (2001). Adenoassociated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity. J Virol 75: 6884-6893. (Pubitemid 32641575)
136. Govindasamy, L, Padron, E, McKenna, R, Muzyczka, N, Kaludov, N, Chiorini, JA et al. (2006). Structurally mapping the diverse phenotype of adeno-associated virus serotype 4. J Virol 80: 11556-11570. (Pubitemid 44788870)
137. Walters, RW, Yi, SM, Keshavjee, S, Brown, KE, Welsh, MJ, Chiorini, JA et al. (2001). Binding of adeno-associated virus type 5 to 2,3-linked sialic acid is required for gene transfer. J Biol Chem 276: 20610-20616.
138. Di Pasquale, G, Davidson, BL, Stein, CS, Martins, I, Scudiero, D, Monks, A et al. (2003). Identification of PDGFR as a receptor for AAV-5 transduction. Nat Med 9: 1306-1312. (Pubitemid 37279855)
139. Walters, RW, Agbandje-McKenna, M, Bowman, VD, Moninger, TO, Olson, NH, Seiler, M et al. (2004). Structure of adeno-associated virus serotype 5. J Virol 78: 3361-3371. (Pubitemid 38568277)
140. Gao, G, Lu, Y, Calcedo, R, Grant, RL, Bell, P, Wang, L et al. (2006). Biology of AAV serotype vectors in liver-directed gene transfer to nonhuman primates. Mol Ther 13: 77-87. (Pubitemid 41763485)
141. Wang, L, Louboutin, JP, Bell, P, Greig, JA, Li, Y, Wu, D et al. (2011). Muscle-directed gene therapy for hemophilia B with more efficient and less immunogenic AAV vectors. J Thromb Haemost 9: 2009-2019.