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Gene and Cell Therapy: Biology and Applications pp 29–56Cite as

Adeno-associated Virus Vectors in Gene Therapy

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Abstract

Adeno-associated virus (AAV) is a member of Parvoviridae family and the genus Dependovirus. To date 13 different serotypes (AAV1 to AAV13) and > 100 variants have been reported from nonhuman primates. The nonpathogenic nature of this virus, the persistence of viral infection in dividing and nondividing cells, and the availability of multiple serotypes have enhanced the utility of AAV for diverse applications in the field of gene therapy. However, their recent success in the clinic has also underlined certain host- and vector-related immune barriers to its optimal utilization in humans. It is thus necessary to understand factors that govern AAV infection in the host cell and the consequent cellular responses. This chapter will review this aspect of AAV-host cellular interactions and outline current developments in generating improved AAV vector systems for human gene therapy applications.

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References

  1. Atchison RW, Casto BC, Hammon WM (1965) Adenovirus-associated defective virus particles. Science 149:754–756

    Article  PubMed  CAS  Google Scholar 

  2. Parks WP, Casazza AM, Alcott J, Melnick JL (1968) Adeno-associated satellite virus interference with the replication of its helper adenovirus. J Exp Med 127:91–108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Hoggan MD, Blacklow NR, Rowe WP (1966) Studies of small DNA viruses found in various adenovirus preparations – physical biological and immunological characteristics. Proc Natl Acad Sci USA 55:1467

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Rose JA, Hoggan MD, Shatkin AJ (1966) Nucleic acid from an adeno-associated virus: chemical and physical studies. Proc Natl Acad Sci USA 56:86–92

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Mayor HD, Jordan L, Ito M (1969) Deoxyribonucleic acid of Adeno-associated satellite virus. J Virol 4:191

    PubMed  PubMed Central  CAS  Google Scholar 

  6. Rose JA, Berns KI, Hoggan MD, Koczot FJ (1969) Evidence for a single-stranded adenovirus-associated virus genome: formation of a DNA density hybrid on release of viral DNA. Proc Natl Acad Sci USA 64:863–869

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Hermonat PL, Muzyczka N (1984) Use of Adeno-associated virus as a mammalian DNA cloning vector - transduction of neomycin resistance into mammalian tissue-culture cells. Proc Natl Acad Sci USA 81:6466–6470

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Ginn SL, Alexander IE, Edelstein ML, Abedi MR, Wixon J (2013) Gene therapy clinical trials worldwide to 2012 an update. J Gene Med 15:65–77

    Article  PubMed  CAS  Google Scholar 

  9. Wagner JA, Messner AH, Moran ML, Daifuku R, Kouyama K, Desch JK, Manley S, Norbash AM, Conrad CK, Friborg S et al (1999) Safety and biological efficacy of an adeno-associated virus vector cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Laryngoscope 109:266–274

    Article  PubMed  CAS  Google Scholar 

  10. Gaudet D, Methot J, Dery S, Brisson D, Essiembre C, Tremblay G, Tremblay K, de Wal J, Twisk J, van den Bulk N et al (2013) Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther 20:361–369

    Article  PubMed  CAS  Google Scholar 

  11. Kaminski R, Bella R, Yin C, Otte J, Ferrante P, Gendelman HE, Li H, Booze R, Gordon J, Hu W, Khalili K (2016) Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. Gene Ther 23:690–695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Balakrishnan B, Jayandharan GR (2014) Basic biology of Adeno-associated virus (AAV) vectors used in gene therapy. Curr Gene Ther 14:86–100

    Article  PubMed  CAS  Google Scholar 

  13. Daya S, Berns KI (2008) Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev 21:583–593

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Carter BJ (2004) Adeno-associated virus and the development of adeno-associated virus vectors: a historical perspective. Mol Ther 10:981–989

    Article  PubMed  CAS  Google Scholar 

  15. Mingozzi F, High KA (2011) Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet 12:341–355

    Article  PubMed  CAS  Google Scholar 

  16. Kotin RM (2011) Large-scale recombinant adeno-associated virus production. Hum Mol Genet 20:R2–R6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Sonntag F, Kother K, Schmidt K, Weghofer M, Raupp C, Nieto K, Kuck A, Gerlach B, Bottcher B, Muller OJ et al (2011) The assembly-activating protein promotes capsid assembly of different Adeno-associated virus serotypes. J Virol 85:12686–12697

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Tseng YS, Agbandje-McKenna M (2014) Mapping the AAV capsid host antibody response toward the development of second generation gene delivery vectors. Front Immunol 5

    Google Scholar 

  19. Lochrie MA, Tatsuno GP, Christie B, McDonnell JW, Zhou SZ, Surosky R, Pierce GF, Colosi P (2006) Mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization. J Virol 80:821–834

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. McCraw DM, O’Donnell JK, Taylor KA, Stagg SM, Chapman MS (2012) Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20. Virology 431:40–49

    Article  PubMed  CAS  Google Scholar 

  21. Gurda BL, DiMattia MA, Miller EB, Bennett A, McKenna R, Weichert WS, Nelson CD, Chen WJ, Muzyczka N, Olson NH et al (2013) Capsid antibodies to different adeno-associated virus serotypes bind common regions. J Virol 87:9111–9124

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Govindasamy L, DiMattia MA, Gurda BL, Halder S, McKenna R, Chiorini JA, Muzyczka N, Zolotukhin S, Agbandje-McKenna M (2013) Structural insights into Adeno-associated virus serotype 5. J Virol 87:11187–11199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Halder S, Nam HJ, Govindasamy L, Vogel M, Dinsart C, Salome N, McKenna R, Agbandje-McKenna M (2013) Structural characterization of H-1 parvovirus: comparison of infectious Virions to empty capsids. J Virol 87:5128–5140

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Opie SR, Warrington KH Jr, Agbandje-McKenna M, Zolotukhin S, Muzyczka N (2003) Identification of amino acid residues in the capsid proteins of adeno-associated virus type 2 that contribute to heparan sulfate proteoglycan binding. J Virol 77:6995–7006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Summerford C, Samulski RJ (1998) Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 72:1438–1445

    PubMed  PubMed Central  CAS  Google Scholar 

  26. Ling C, Lu Y, Cheng BB, McGoogan KE, Gee SWY, Ma WQ, Li BZ, Aslanidi GV, Srivastava A (2011) High-efficiency transduction of liver Cancer cells by recombinant Adeno-associated virus serotype 3 vectors. J Vis Exp

    Google Scholar 

  27. Di Pasquale G, Davidson BL, Stein CS, Martins IS, Scudiero D, Monks A, Chiorini JA (2003) Identification of PDGFR as a receptor for AAV-5 transduction. Nat Med 9:1306–1312

    Article  PubMed  CAS  Google Scholar 

  28. Wu Z, Miller E, Agbandje–McKenna M, Samulski RJ (2006) Alpha2,3 and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6. J Virol 80:9093–9103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Wu ZJ, Asokan A, Samulski RJ (2006) Adeno-associated virus serotypes: vector toolkit for human gene therapy. Mol Ther 14:316–327

    Article  PubMed  CAS  Google Scholar 

  30. Shen S, Bryant KD, Brown SM, Randell SH, Asokan A (2011) Terminal N-linked galactose is the primary receptor for Adeno-associated virus 9. J Biol Chem 286:13532–13540

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Sanlioglu S, Benson PK, Yang J, Atkinson EM, Reynolds T, Engelhardt JF (2000) Endocytosis and nuclear trafficking of adeno-associated virus type 2 are controlled by rac1 and phosphatidylinositol-3 kinase activation. J Virol 74:9184–9196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Duan D, Li Q, Kao AW, Yue Y, Pessin JE, Engelhardt JF (1999) Dynamin is required for recombinant adeno-associated virus type 2 infection. J Virol 73:10371–10376

    PubMed  PubMed Central  CAS  Google Scholar 

  33. Nonnenmacher M, Weber T (2011) Adeno-associated virus 2 infection requires endocytosis through the CLIC/GEEC pathway. Cell Host Microbe 10:563–576

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Johnson JS, Samulski RJ (2009) Enhancement of Adeno-associated virus infection by mobilizing capsids into and out of the nucleolus. J Virol 83:2632–2644

    Article  PubMed  CAS  Google Scholar 

  35. Bartlett JS, Wilcher R, Samulski RJ (2000) Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors. J Virol 74:2777–2785

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Akache B, Grimm D, Pandey K, Yant SR, Xu H, 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Girod A, Wobus CE, Zadori Z, Ried M, Leike K, Tijssen P, Kleinschmidt JA, Hallek M (2002) The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. J Gen Virol 83:973–978

    Article  PubMed  CAS  Google Scholar 

  38. Chang LS, Shi Y, Shenk T (1989) Adeno-associated virus P5 promoter contains an adenovirus E1a-inducible element and a binding-site for the major late transcription factor. J Virol 63:3479–3488

    PubMed  PubMed Central  CAS  Google Scholar 

  39. Duan DS, Sharma P, Dudus L, Zhang YL, Sanlioglu S, Yan ZY, Yue YP, Ye YH, Lester R, Yang J et al (1999) Formation of adeno-associated virus circular genomes is differentially regulated by adenovirus E4 ORF6 and E2a gene expression. J Virol 73:161–169

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Yalkinoglu AO, Heilbronn R, Burkle A, Schlehofer JR, Hausen HZ (1988) DNA amplification of Adeno-associated virus as a response to cellular Genotoxic stress. Cancer Res 48:3123–3129

    PubMed  CAS  Google Scholar 

  41. Sanlioglu S, Duan DS, Engelhardt JF (1999) Two independent molecular pathways for recombinant adeno-associated virus genome conversion occur after UV-C and E4orf6 augmentation of transduction. Hum Gene Ther 10:591–602

    Article  PubMed  CAS  Google Scholar 

  42. Berns KI (1990) Parvovirus replication. Microbiol Rev 54:316–329

    PubMed  PubMed Central  CAS  Google Scholar 

  43. Ruffing M, Zentgraf H, Kleinschmidt JA (1992) Assembly of viruslike particles by recombinant structural proteins of adeno-associated virus type 2 in insect cells. J Virol 66:6922–6930

    PubMed  PubMed Central  CAS  Google Scholar 

  44. Wistuba A, Kern A, Weger S, Grimm D, Kleinschmidt JA (1997) Subcellular compartmentalization of adeno-associated virus type 2 assembly. J Virol 71:1341–1352

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Daya S, Cortez N, Berns KI (2009) Adeno-associated virus site-specific integration is mediated by proteins of the nonhomologous end-joining pathway. J Virol 83:11655–11664

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Berns KI, Pinkerton TC, Thomas GF, Hoggan MD (1975) Detection of adeno-associated virus (AAV)-specific nucleotide sequences in DNA isolated from latently infected Detroit 6 cells. Virology 68:556–560

    Article  PubMed  CAS  Google Scholar 

  47. Giraud C, Winocour E, Berns KI (1994) Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence. Proc Natl Acad Sci USA 91:10039–10043

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Balague C, Kalla M, Zhang WW (1997) Adeno-associated virus Rep78 protein and terminal repeats enhance integration of DNA sequences into the cellular genome. J Virol 71:3299–3306

    PubMed  PubMed Central  CAS  Google Scholar 

  49. Recchia A, Mavilio F (2011) Site-specific integration by the adeno-associated virus rep protein. Curr Gene Ther 11:399–405

    Article  PubMed  CAS  Google Scholar 

  50. Philpott NJ, Gomos J, Berns KI, Falck-Pedersen E (2002) A p5 integration efficiency element mediates rep-dependent integration into AAVS1 at chromosome 19. Proc Natl Acad Sci USA 99:12381–12385

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. McCarty DM, Young SM Jr, Samulski RJ (2004) Integration of adeno-associated virus (AAV) and recombinant AAV vectors. Annu Rev Genet 38:819–845

    Article  PubMed  CAS  Google Scholar 

  52. Gao GP, Alvira MR, Somanathan S, Lu Y, Vandenberghe LH, Rux JJ, Calcedo R, Sanmiguel J, Abbas Z, Wilson JM (2003) Adeno-associated viruses undergo substantial evolution in primates during natural infections. Proc Natl Acad Sci USA 100:6081–6086

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  53. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE (2008) Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther 16:1073–1080

    Article  PubMed  CAS  Google Scholar 

  54. Pillay S, Meyer NL, Puschnik AS, Davulcu O, Diep J, Ishikawa Y, Jae LT, Wosen JE, Nagamine CM, Chapman MS, Carette JE (2016) An essential receptor for adeno-associated virus infection. Nature 530:108–112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Pfeifer A, Verma IM (2001) Gene therapy: promises and problems. Annu Rev Genomics Hum Genet 2:177–211

    Article  PubMed  CAS  Google Scholar 

  56. Asokan A, Schaffer DV, Samulski RJ (2012) The AAV vector toolkit: poised at the clinical crossroads. Mol Ther 20:699–708

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Ferrari FK, Samulski T, Shenk T, Samulski RJ (1996) Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors. J Virol 70:3227–3234

    PubMed  PubMed Central  CAS  Google Scholar 

  58. Nathwani AC, Gray JT, Ng CYC, Zhou JF, Spence Y, Waddington SN, Tuddenham EGD, Kemball-Cook G, McIntosh J, Boon-Spijker M 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Nakai H, Fuess S, Storm TA, Muramatsu S, Nara Y, Kay MA (2005) Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in mice. J Virol 79:214–224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Gao GP, Vandenberghe LH, Alvira MR, Lu Y, Calcedo R, Zhou XY, Wilson JA (2004) Clades of Adeno-associated viruses are widely disseminated in human tissues. J Virol 78:6381–6388

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Blankinship MJ, Gregorevic P, Allen JM, Harper SQ, Harper H, Halbert CL, Miller AD, Chamberlain JS (2004) Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6. Mol Ther 10:671–678

    Article  PubMed  CAS  Google Scholar 

  62. Lebherz C, Maguire A, Tang W, Bennett J, Wilson JM (2008) Novel AAV serotypes for improved ocular gene transfer. J Gene Med 10:375–382

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Davidson BL, Stein CS, Heth JA, Martins I, Kotin RM, Derksen TA, Zabner J, Ghodsi A, Chiorini JA (2000) Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system. Proc Natl Acad Sci USA 97:3428–3432

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  64. Vincent KA, Piraino ST, Wadsworth SC (1997) Analysis of recombinant adeno-associated virus packaging and requirements for rep and cap gene products. J Virol 71:1897–1905

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Grimm D, Kern A, Rittner K, Kleinschmidt JA (1998) Novel tools for production and purification of recombinant adenoassociated virus vectors. Hum Gene Ther 9:2745–2760

    Article  PubMed  CAS  Google Scholar 

  66. Lock M, Alvira M, Vandenberghe LH, Samanta A, Toelen J, Debyser Z, Wilson JM (2010) Rapid, simple, and versatile manufacturing of recombinant Adeno-associated viral vectors at scale. Hum Gene Ther 21:1259–1271

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Ling C, Lu YA, Kalsi JK, Jayandharan GR, Li BZ, Ma WQ, Cheng BB, Gee SWY, McGoogan KE, Govindasamy L et al (2010) Human hepatocyte growth factor receptor is a cellular Coreceptor for Adeno-associated virus serotype. Hum Gene Ther 21:1741–1747

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Rabinowitz JE, Samulski J (1998) Adeno-associated virus expression systems for gene transfer. Curr Opin Biotechnol 9:470–475

    Article  PubMed  CAS  Google Scholar 

  69. Ayuso E, Mingozzi F, Montane J, Leon X, Anguela XM, Haurigot V, Edmonson SA, Africa L, Zhou S, High KA et al (2010) High AAV vector purity results in serotype- and tissue-independent enhancement of transduction efficiency. Gene Ther 17:503–510

    Article  PubMed  CAS  Google Scholar 

  70. Flotte T, Carter B, Conrad C, Guggino W, Reynolds T, Rosenstein B, Taylor G, Walden S, Wetzel R (1996) A phase I study of an adeno-associated virus-CFTR gene vector in adult CF patients with mild lung disease. Hum Gene Ther 7:1145–1159

    Article  PubMed  CAS  Google Scholar 

  71. Lee H, Lotery A (2017) Gene therapy for RPE65-mediated inherited retinal dystrophy completes phase 3. Lancet 390:823–824

    Article  PubMed  Google Scholar 

  72. Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Della Peruta M, Lheriteau E, Patel N, Raj D et al (2014) Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 371:1994–2004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Ramos J, Chamberlain JS (2015) Gene therapy for Duchenne muscular dystrophy. Expert Opin Orphan Drugs 3:1255–1266

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM et al (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med 358:2240–2248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Cideciyan AV, Hauswirth WW, Aleman TS, Kaushal S, Schwartz SB, Boye SL, Windsor EAM, Conlon TJ, Sumaroka A, Pang JJ et al (2009) Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum Gene Ther 20:999–1004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM 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

    Article  PubMed  CAS  Google Scholar 

  77. Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B et al (2006) Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med 12:342–347

    Article  PubMed  CAS  Google Scholar 

  78. Mingozzi F, Maus MV, Hui DJ, Sabatino DE, Murphy SL, Rasko JE, Ragni MV, Manno CS, Sommer J, Jiang H et al (2007) CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat Med 13:419–422

    Article  PubMed  CAS  Google Scholar 

  79. Gaudet D, Methot J, Kastelein J (2012) Gene therapy for lipoprotein lipase deficiency. Curr Opin Lipidol 23:310–320

    Article  PubMed  CAS  Google Scholar 

  80. Flotte TR (2004) Immune responses to recombinant adeno-associated virus vectors: putting preclinical findings into perspective. Hum Gene Ther 15:716–717

    Article  PubMed  CAS  Google Scholar 

  81. Mingozzi F, High KA (2011) Immune responses to AAV in clinical trials. Curr Gene Ther 11:321–330

    Article  PubMed  CAS  Google Scholar 

  82. Rogers GL, Martino AT, Aslanidi GV, Jayandharan GR, Srivastava A, Herzog RW (2011) Innate Immune Responses to AAV Vectors. Front Microbiol 2:194

    Article  PubMed  PubMed Central  Google Scholar 

  83. Zaiss AK, Cotter MJ, White LR, Clark SA, Wong NC, Holers VM, Bartlett JS, Muruve DA (2008) Complement is an essential component of the immune response to adeno-associated virus vectors. J Virol 82:2727–2740

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Zaiss AK, Muruve DA (2005) Immune responses to adeno-associated virus vectors. Curr Gene Ther 5:323–331

    Article  PubMed  CAS  Google Scholar 

  85. Zhu J, Huang X, Yang Y (2009) The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice. J Clin Invest 119:2388–2398

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Suzuki M, Bertin TK, Rogers GL, Cela RG, Zolotukhin I, Palmer DJ, Ng P, Herzog RW, Lee B (2013) Differential type I interferon-dependent transgene silencing of helper-dependent adenoviral vs. adeno-associated viral vectors in vivo. Mol Ther 21:796–805

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Martino AT, Suzuki M, Markusic DM, Zolotukhin I, Ryals RC, Moghimi B, Ertl HC, Muruve DA, Lee B, Herzog RW (2011) The genome of self-complementary adeno-associated viral vectors increases toll-like receptor 9-dependent innate immune responses in the liver. Blood 117:6459–6468

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Hosel M, Broxtermann M, Janicki H, Esser K, Arzberger S, Hartmann P, Gillen S, Kleeff J, Stabenow D, Odenthal M et al (2012) Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors. Hepatology 55:287–297

    Article  PubMed  CAS  Google Scholar 

  89. Hu P, Han Z, Couvillon AD, Kaufman RJ, Exton JH (2006) Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1 alpha-mediated NF-kappa B activation and down-regulation of TRAF2 expression. Mol Cell Biol 26:3071–3084

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Murphy SL, Li H, Zhou S, Schlachterman A, High KA (2008) Prolonged susceptibility to antibody-mediated neutralization for adeno-associated vectors targeted to the liver. Mol Ther 16:138–145

    Article  PubMed  CAS  Google Scholar 

  91. Amado D, Mingozzi F, Hui D, Bennicelli JL, Wei Z, Chen Y, Bote E, Grant RL, Golden JA, Narfstrom K et al (2010) Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness. Sci Transl Med 2:21ra16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Calcedo R, Vandenberghe LH, Gao G, Lin J, Wilson JM (2009) Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis 199:381–390

    Article  PubMed  Google Scholar 

  93. Chirmule N, Xiao W, Truneh A, Schnell MA, Hughes JV, Zoltick P, Wilson JM (2000) Humoral immunity to adeno-associated virus type 2 vectors following administration to murine and nonhuman primate muscle. J Virol 74:2420–2425

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Mills DM, Cambier JC (2003) B lymphocyte activation during cognate interactions with CD4+ T lymphocytes: molecular dynamics and immunologic consequences. Semin Immunol 15:325–329

    Article  PubMed  CAS  Google Scholar 

  95. Mingozzi F, Anguela XM, Pavani G, Chen Y, Davidson RJ, Hui DJ, Yazicioglu M, Elkouby L, Hinderer CJ, Faella A et al (2012) Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med 5:194ra192

    Google Scholar 

  96. Mingozzi F, Chen Y, Murphy SL, Edmonson SC, Tai A, Price SD, Metzger ME, Zhou S, Wright JF, Donahue RE et al (2012) Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol Ther 20:1410–1416

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Calcedo R, Wilson JM (2013) Humoral immune response to AAV. Front Immunol 4

    Google Scholar 

  98. Mingozzi F, High KA (2013) Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood 122:23–36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Wang LL, Calcedo R, Bell P, Lin JP, Grant RL, Siegel DL, Wilson JM (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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Lisowski L, Tay SS, Alexander IE (2015) Adeno-associated virus serotypes for gene therapeutics. Curr Opin Pharmacol 24:59–67

    Article  PubMed  CAS  Google Scholar 

  101. Vandenberghe LH, Wilson JM, Gao G (2009) Tailoring the AAV vector capsid for gene therapy. Gene Ther 16:311–319

    Article  PubMed  CAS  Google Scholar 

  102. Buning H, Huber A, Zhang L, Meumann N, Hacker U (2015) Engineering the AAV capsid to optimize vector-host-interactions. Curr Opin Pharmacol 24:94–104

    Article  PubMed  CAS  Google Scholar 

  103. Hirsch ML, Agbandje-McKenna M, Samulski RJ (2010) Little vector, big gene transduction: fragmented genome reassembly of Adeno-associated virus. Mol Ther 18:6–8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Kwon I, Schaffer DV (2008) Designer gene delivery vectors: molecular engineering and evolution of adeno-associated viral vectors for enhanced gene transfer. Pharm Res 25:489–499

    Article  PubMed  CAS  Google Scholar 

  105. Waehler R, Russell SJ, Curiel DT (2007) Engineering targeted viral vectors for gene therapy. Nat Rev Genet 8:573–587

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  106. Buning H, Perabo L, Coutelle O, Quadt-Humme S, Hallek M (2008) Recent developments in adeno-associated virus vector technology. J Gene Med 10:717–733

    Article  PubMed  CAS  Google Scholar 

  107. Kienle E, Sens E, Borner K, Niopek D, Wiedtke E, Grosse S, Grimm D (2012) Engineering and evolution of synthetic Adeno-associated virus (AAV) gene therapy vectors via DNA family shuffling. J Visual Exp

    Google Scholar 

  108. Bartel M, Schaffer D, Buning H (2011) Enhancing the clinical potential of AAV vectors by capsid engineering to evade pre-existing immunity. Front Microbiol 2

    Google Scholar 

  109. Muller OJ, Kaul F, Weitzman MD, Pasqualini R, Arap W, Kleinschmidt JA, Trepel M (2003) Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nat Biotechnol 21:1040–1046

    Article  PubMed  CAS  Google Scholar 

  110. Flotte TR (2000) Size does matter: overcoming the adeno-associated virus packaging limit. Respir Res 1:16–18

    Google Scholar 

  111. Wu ZJ, Yang HY, Colosi P (2010) Effect of genome size on AAV vector packaging. Mol Ther 18:80–86

    Article  PubMed  CAS  Google Scholar 

  112. Yan ZY, Zhang YL, Duan DS, Engelhardt JF (2000) Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy. Proc Natl Acad Sci USA 97:6716–6721

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  113. Li CW, Goudy K, Hirsch M, Asokan A, Fan Y, Alexander J, Sun JJ, Monahan P, Seiber D, Sidney J et al (2009) Cellular immune response to cryptic epitopes during therapeutic gene transfer. Proc Natl Acad Sci USA 106:10770–10774

    Article  PubMed  PubMed Central  Google Scholar 

  114. Fisher KJ, Gao GP, Weitzman MD, DeMatteo R, Burda JF, Wilson JM (1996) Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis. J Virol 70:520–532

    PubMed  PubMed Central  CAS  Google Scholar 

  115. McCarty DM, Monahan PE, Samulski RJ (2001) Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther 8:1248–1254

    Article  PubMed  CAS  Google Scholar 

  116. McCarty DM, Fu H, Monahan PE, Toulson CE, Naik P, Samulski RJ (2003) Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther 10:2112–2118

    Article  PubMed  CAS  Google Scholar 

  117. Wu J, Zhao W, Zhong L, Han Z, Li B, Ma W, Weigel-Kelley KA, Warrington KH, Srivastava A (2007) Self-complementary recombinant adeno-associated viral vectors: packaging capacity and the role of rep proteins in vector purity. Hum Gene Ther 18:171–182

    Article  PubMed  CAS  Google Scholar 

  118. Kotterman MA, Schaffer DV (2014) Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet 15:445–451

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Zhong L, Li B, Mah CS, Govindasamy L, Agbandje-McKenna M, Cooper M, Herzog RW, Zolotukhin I, Warrington KH Jr, Weigel-Van Aken KA 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

    Article  PubMed  PubMed Central  Google Scholar 

  120. Petrs-Silva H, Dinculescu A, Li Q, Deng WT, Pang JJ, Min SH, Chiodo V, Neeley AW, Govindasamy L, Bennett A et al (2011) Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Mol Ther 19:293–301

    Article  PubMed  CAS  Google Scholar 

  121. Sen D, Balakrishnan B, Gabriel N, Agrawal P, Roshini V, Samuel R, Srivastava A, Jayandharan GR (2013) Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy. Sci Rep 3

    Google Scholar 

  122. Gabriel N, Hareendran S, Sen D, Gadkari RA, Sudha G, Selot R, Hussain M, Dhaksnamoorthy R, Samuel R, Srinivasan N et al (2013) Bioengineering of AAV2 capsid at specific serine, threonine, or lysine residues improves its transduction efficiency in vitro and in vivo. Hum Gene Ther Methods 24:80–93

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Sen D, Gadkari RA, Sudha G, Gabriel N, Kumar YS, Selot R, Samuel R, Rajalingam S, Ramya V, Nair SC et al (2013) Targeted modifications in adeno-associated virus serotype 8 capsid improves its hepatic gene transfer efficiency in vivo. Hum Gene Ther Methods 24:104–116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Ling C, Wang Y, Lu Y, Wang L, Jayandharan GR, Aslanidi GV, Li B, Cheng B, Ma W, Lentz T et al (2015) Enhanced transgene expression from recombinant single-stranded D-sequence-substituted adeno-associated virus vectors in human cell lines in vitro and in murine hepatocytes in vivo. J Virol 89:952–961

    Article  PubMed  CAS  Google Scholar 

  125. Koerber JT, Klimczak R, Jang JH, Dalkara D, Flannery JG, Schaffer DV (2009) Molecular evolution of adeno-associated virus for enhanced glial gene delivery. Mol Ther 17:2088–2095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Selot RS, Hareendran S, Jayandharan GR (2014) Developing immunologically inert adeno-associated virus (AAV) vectors for gene therapy: possibilities and limitations. Curr Pharm Biotechnol 14:1072–1082

    Article  PubMed  CAS  Google Scholar 

  127. Hoffman BE, Martino AT, Sack BK, Cao O, Liao G, Terhorst C, Herzog RW (2011) Nonredundant roles of IL-10 and TGF-beta in suppression of immune responses to hepatic AAV-factor IX gene transfer. Mol Ther 19:1263–1272

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. De Groot AS, Moise L, McMurry JA, Wambre E, Van Overtvelt L, Moingeon P, Scott DW, Martin W (2008) Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes". Blood 112:3303–3311

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Kay MA, Meuse L, Gown AM, Linsley P, Hollenbaugh D, Aruffo A, Ochs HD, Wilson CB (1997) Transient immunomodulation with anti-CD40 ligand antibody and CTLA4Ig enhances persistence and secondary adenovirus-mediated gene transfer into mouse liver. Proc Natl Acad Sci USA 94:4686–4691

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  130. Seregin SS, Appledorn DM, McBride AJ, Schuldt NJ, Aldhamen YA, Voss T, Wei J, Bujold M, Nance W, Godbehere S, Amalfitano A (2009) Transient pretreatment with glucocorticoid ablates innate toxicity of systemically delivered adenoviral vectors without reducing efficacy. Mol Ther 17:685–696

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Russell DW, Hirata RK (1998) Human gene targeting by viral vectors. Nat Genet 18:325–330

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Russell DW, Hirata RK (2008) Human gene targeting favors insertions over deletions. Hum Gene Ther 19:907–914

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Vasileva A, Jessberger R (2005) Precise hit: Adeno-associated virus in gene targeting. Nat Rev Microbiol 3:837–847

    Article  PubMed  CAS  Google Scholar 

  134. Hirata RK, Russell DW (2000) Design and packaging of adeno-associated virus gene targeting vectors. J Virol 74:4612–4620

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Li HJ, Haurigot V, Doyon Y, Li TJ, Wong SNY, Bhagwat AS, Malani N, Anguela XM, Sharma R, Ivanciu L et al (2011) In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature 475:217–U128

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Rivera RMC, Madhavan S, Pan XF, Ran FA, Yan WX et al (2016) In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351:403–407

    Article  PubMed  CAS  Google Scholar 

  137. Deveau H, Garneau JE, Moineau S (2010) CRISPR/Cas system and its role in phage-Bacteria interactions. Annu Rev Microbiol 64(64):475–493

    Article  PubMed  CAS  Google Scholar 

  138. Cong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, Hsu PD, Wu XB, Jiang WY, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Makarova KS, Haft DH, Barrangou R, Brouns SJJ, Charpentier E, Horvath P, Moineau S, Mojica FJM, Wolf YI, Yakunin AF et al (2011) Evolution and classification of the CRISPR-Cas systems. Nat Rev Microbiol 9:467–477

    Article  PubMed  CAS  Google Scholar 

  140. Doudna JA, Charpentier E (2014) Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346:1258096

    Article  PubMed  CAS  Google Scholar 

  141. Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J, Charpentier E (2011) CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471:602–607

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Overballe-Petersen S, Harms K, Orlando LAA, Mayar JVM, Rasmussen S, Dahl TW, Rosing MT, Poole AM, Sicheritz-Ponten T, Brunak S et al (2013) Bacterial natural transformation by highly fragmented and damaged DNA. Proc Natl Acad Sci USA 110:19860–19865

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  143. Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng ZL, Gonzales APW, Li ZY, Peterson RT, Yeh JRJ et al (2015) Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523:481–U249

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, Lim WA (2013) Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152:1173–1183

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y, Zhang F (2013) Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154:1380–1389

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Jiang WY, Bikard D, Cox D, Zhang F, Marraffini LA (2013) RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol 31:233–239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biological Sciences and Bioengineering, IIT-Kanpur, Kanpur, Uttar Pradesh, India

    Bertin Mary, Nusrat Khan, Sathyathithan Arumugam, Himanshi Saxena, Mohit Kumar, Paramasivam Manimaran, Sourav Chattopadhyay & G. R. Jayandharan

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  1. Bertin Mary
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  2. Nusrat Khan
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    Giridhara R. Jayandharan

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Mary, B. et al. (2018). Adeno-associated Virus Vectors in Gene Therapy. In: Jayandharan, G. (eds) Gene and Cell Therapy: Biology and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-13-0481-1_2

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