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Helper-dependent adenoviral vectors

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Gene Therapy for Autoimmune and Inflammatory Diseases

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

Helper-dependent adenoviral (HDAd) vectors have several characteristics making them attractive for human gene therapy. These vectors are completely devoid of viral coding sequences and are able to mediate high efficiency transduction in vivo to direct high level transgene expression with negligible chronic toxicity. However, clinical translation is complicated by the dose-dependent acute toxic response following systemic vector injection. With a better understanding of vector-mediated toxicity and improved delivery methods, |HDAds may emerge as an important vector for gene therapy of human diseases.

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References

  1. Gene Therapy Clinical Trials Worldwide. Journal of Gene Medicine. Available at www.wiley.co.uk/genmed/clinical (accessed April 2009)

    Google Scholar 

  2. Segura MM, Alba R, Bosch A, Chillon M (2008) Advances in helper-dependent adenoviral vector research. Curr Gene Ther 8: 222–235

    Article  CAS  PubMed  Google Scholar 

  3. Brunetti-Pierri N, Ng P (2008) Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors. Gene Ther 15: 553–560

    Article  CAS  PubMed  Google Scholar 

  4. Parks RJ, Chen L, Anton M, Sankar U, Rudnicki MA, Graham FL (1996) A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc Natl Acad Sci USA 93: 13565–13570

    Article  CAS  PubMed  Google Scholar 

  5. Bett AJ, Prevec L, Graham FL (1993) Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 67: 5911–5921

    CAS  PubMed  Google Scholar 

  6. Parks RJ, Graham FL (1997) A helper-dependent system for adenovirus vector production helps define a lower limit for efficient DNA packaging. J Virol 71: 3293–3298

    CAS  PubMed  Google Scholar 

  7. Palmer D, Ng P (2007) Methods for the production and characterization of helper-dependent adenoviral vectors. Cold Spring Harbor Press

    Google Scholar 

  8. Kim IH, Jozkowicz A, Piedra PA, Oka K, Chan L (2001) Lifetime correction of genetic deficiency in mice with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci USA 98: 13282–13287

    Article  CAS  PubMed  Google Scholar 

  9. Toietta G, Mane VP, Norona WS, Finegold MJ, Ng P, McDonagh AF, Beaudet AL, Lee B (2005) Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helperdependent adenoviral vector. Proc Natl Acad Sci USA 102: 3930–3935

    Article  CAS  PubMed  Google Scholar 

  10. Brunetti-Pierri N, Stapleton GE, Palmer DJ, Zuo Y, Mane VP, Finegold MJ, Beaudet AL, Leland MM, Mullins CE, Ng P (2007) Pseudo-hydrodynamic delivery of helper-dependent adenoviral vectors into non-human primates for liver-directed gene therapy. Mol Ther 15: 732–740

    CAS  PubMed  Google Scholar 

  11. Brunetti-Pierri N, Ng T, Iannitti DA, Palmer DJ, Beaudet AL, Finegold MJ, Carey KD, Cioffi WG, Ng P (2006) Improved hepatic transduction, reduced systemic vector dissemination, and longterm transgene expression by delivering helper-dependent adenoviral vectors into the surgically isolated liver of nonhuman primates. Hum Gene Ther 17: 391–404

    Article  CAS  PubMed  Google Scholar 

  12. Morral N, O’Neal W, Rice K, Leland M, Kaplan J, Piedra PA, Zhou H, Parks RJ, Velji R, Aguilar-Cordova E et al. (1999) Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proc Natl Acad Sci USA 96: 12816–12821

    Article  CAS  PubMed  Google Scholar 

  13. Brunetti-Pierri N, Stapleton GE, Law M, Breinholt J, Palmer DJ, Zuo Y, Grove NC, Finegold MJ, Rice K, Beaudet AL et al. (2009) Efficient, long-term hepatic gene transfer using clinically relevant HDAd doses by balloon occlusion catheter delivery in nonhuman primates. Mol Ther 17: 327–333

    Article  CAS  PubMed  Google Scholar 

  14. Brunetti-Pierri N, Nichols TC, McCorquodale S, Merricks E, Palmer DJ, Beaudet AL, Ng P (2005) Sustained phenotypic correction of canine hemophilia B after systemic administration of helper-dependent adenoviral vector. Hum Gene Ther 16: 811–820

    Article  CAS  PubMed  Google Scholar 

  15. Kojima H, Fujimiya M, Matsumura K, Younan P, Imaeda H, Maeda M, Chan L (2003) NeuroDbetacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 9: 596–603

    Article  CAS  PubMed  Google Scholar 

  16. Ruiz R, Witting SR, Saxena R, Morral N (2009) Robust hepatic gene silencing for functional studies using helper-dependent adenovirus vectors. Hum Gene Ther 20: 87–94

    Article  CAS  PubMed  Google Scholar 

  17. Witting SR, Brown M, Saxena R, Nabinger S, Morral N (2008) Helper-dependent adenovirusmediated short hairpin RNA expression in the liver activates the interferon response. J Biol Chem 283: 2120–2128

    Article  CAS  PubMed  Google Scholar 

  18. Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, Kay MA (2006) Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441: 537–541

    Article  CAS  PubMed  Google Scholar 

  19. Brown BD, Cantore A, Annoni A, Sergi LS, Lombardo A, Della Valle P, D’Angelo A, Naldini L (2007) A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood 110: 4144–4152

    Article  CAS  PubMed  Google Scholar 

  20. Cerullo V, McCormack W, Seiler M, Mane V, Cela R, Clarke C, Rodgers JR, Lee B (2007) Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus. Hum Gene Ther 18: 1215–1224

    Article  CAS  PubMed  Google Scholar 

  21. Mingozzi F, Liu YL, Dobrzynski E, Kaufhold A, Liu JH, Wang Y, Arruda VR, High KA, Herzog RW (2003) Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer. J Clin Invest 111: 1347–1356

    CAS  PubMed  Google Scholar 

  22. Luth S, Huber S, Schramm C, Buch T, Zander S, Stadelmann C, Bruck W, Wraith DC, Herkel J, Lohse AW (2008) Ectopic expression of neural autoantigen in mouse liver suppresses experimental autoimmune neuroinflammation by inducing antigen-specific Tregs. J Clin Invest 118: 3403–3410

    PubMed  Google Scholar 

  23. Tao N, Gao GP, Parr M, Johnston J, Baradet T, Wilson JM, Barsoum J, Fawell SE (2001) Sequestration of adenoviral vector by Kupffer cells leads to a nonlinear dose response of transduction in liver. Mol Ther 3: 28–35

    Article  CAS  PubMed  Google Scholar 

  24. Schiedner G, Hertel S, Johnston M, Dries V, van Rooijen N, Kochanek S (2003) Selective depletion or blockade of Kupffer cells leads to enhanced and prolonged hepatic transgene expression using high-capacity adenoviral vectors. Mol Ther 7: 35–43

    Article  CAS  PubMed  Google Scholar 

  25. Lyons M, Onion D, Green NK, Aslan K, Rajaratnam R, Bazan-Peregrino M, Phipps S, Hale S, Mautner V, Seymour LW et al. (2006) Adenovirus type 5 interactions with human blood cells may compromise systemic delivery. Mol Ther 14: 118–128

    Article  CAS  PubMed  Google Scholar 

  26. Seiradake E, Henaff D, Wodrich H, Billet O, Perreau M, Hippert C, Mennechet F, Schoehn G, Lortat-Jacob H, Dreja H et al. (2009) The cell adhesion molecule “CAR” and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution. PLoS Pathog 5: e1000277

    Article  PubMed  Google Scholar 

  27. Carlisle RC, Di Y, Cerny AM, Sonnen AF, Sim RB, Green NK, Subr V, Ulbrich K, Gilbert RJ, Fisher KD et al. (2009) Human erythrocytes bind and inactivate type 5 adenovirus by presenting coxsackievirus-adenovirus receptor and complement receptor 1. Blood 113: 1909–1918

    Article  CAS  PubMed  Google Scholar 

  28. Muruve DA, Barnes MJ, Stillman IE, Libermann TA (1999) Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo. Hum Gene Ther 10: 965–976

    Article  CAS  PubMed  Google Scholar 

  29. Brunetti-Pierri N, Palmer DJ, Beaudet AL, Carey KD, Finegold M, Ng P (2004) Acute toxicity after high-dose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Hum Gene Ther 15: 35–46

    Article  CAS  PubMed  Google Scholar 

  30. O’Neal WK, Zhou H, Morral N, Aguilar-Cordova E, Pestaner J, Langston C, Mull B, Wang Y, Beaudet AL, Lee B (1998) Toxicological comparison of E2a-deleted and first-generation adenoviral vectors expressing alpha1-antitrypsin after systemic delivery. Hum Gene Ther 9: 1587–1598

    Article  PubMed  Google Scholar 

  31. Wolins N, Lozier J, Eggerman TL, Jones E, Aguilar-Cordova E, Vostal JG (2003) Intravenous administration of replication-incompetent adenovirus to rhesus monkeys induces thrombocytopenia by increasing in vivo platelet clearance. Br J Haematol 123: 903–905

    Article  CAS  PubMed  Google Scholar 

  32. Cichon G, Boeckh-Herwig S, Schmidt HH, Wehnes E, Muller T, Pring-Akerblom P, Burger R (2001) Complement activation by recombinant adenoviruses. Gene Ther 8: 1794–1800

    Article  CAS  PubMed  Google Scholar 

  33. Jiang H, Wang Z, Serra D, Frank MM, Amalfitano A (2004) Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-ad antibodies. Mol Ther 10: 1140–1142

    Article  CAS  PubMed  Google Scholar 

  34. Kiang A, Hartman ZC, Everett RS, Serra D, Jiang H, Frank MM, Amalfitano A (2006) Multiple innate inflammatory responses induced after systemic adenovirus vector delivery depend on a functional complement system. Mol Ther 14: 588–598

    Article  CAS  PubMed  Google Scholar 

  35. Shayakhmetov DM, Gaggar A, Ni S, Li ZY, Lieber A (2005) Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity. J Virol 79: 7478–7491

    Article  CAS  PubMed  Google Scholar 

  36. Parker AL, Waddington SN, Nicol CG, Shayakhmetov DM, Buckley SM, Denby L, Kemball-Cook G, Ni S, Lieber A, McVey JH et al. (2006) Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. Blood 108: 2554–2561

    Article  CAS  PubMed  Google Scholar 

  37. Kalyuzhniy O, Di Paolo NC, Silvestry M, Hofherr SE, Barry MA, Stewart PL, Shayakhmetov DM (2008) Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo. Proc Natl Acad Sci USA 105: 5483–5488

    Article  CAS  PubMed  Google Scholar 

  38. Waddington SN, McVey JH, Bhella D, Parker AL, Barker K, Atoda H, Pink R, Buckley SM, Greig JA, Denby L et al. (2008) Adenovirus serotype 5 hexon mediates liver gene transfer. Cell 132: 397–409

    Article  CAS  PubMed  Google Scholar 

  39. Yotnda P, Chen DH, Chiu W, Piedra PA, Davis A, Templeton NS, Brenner MK (2002) Bilamellar cationic liposomes protect adenovectors from preexisting humoral immune responses. Mol Ther 5: 233–241

    Article  CAS  PubMed  Google Scholar 

  40. Mok H, Palmer DJ, Ng P, Barry MA (2005) Evaluation of polyethylene glycol modification of first-generation and helper-dependent adenoviral vectors to reduce innate immune responses. Mol Ther 11: 66–79

    Article  CAS  PubMed  Google Scholar 

  41. Croyle MA, Le HT, Linse KD, Cerullo V, Toietta G, Beaudet A, Pastore L (2005) PEGylated helper-dependent adenoviral vectors: highly efficient vectors with an enhanced safety profile. Gene Ther 12: 579–587

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  43. Walters RW, Grunst T, Bergelson JM, Finberg RW, Welsh MJ, Zabner J (1999) Basolateral localization of fiber receptors limits adenovirus infection from the apical surface of airway epithelia. J Biol Chem 274: 10219–10226

    Article  CAS  PubMed  Google Scholar 

  44. Yei S, Mittereder N, Wert S, Whitsett JA, Wilmott RW, Trapnell BC (1994) In vivo evaluation of the safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lung. Hum Gene Ther 5: 731–744

    Article  CAS  PubMed  Google Scholar 

  45. Wilmott RW, Amin RS, Perez CR, Wert SE, Keller G, Boivin GP, Hirsch R, De Inocencio J, Lu P, Reising SF et al. (1996) Safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lungs of nonhuman primates. Hum Gene Ther 7: 301–318

    Article  CAS  PubMed  Google Scholar 

  46. Simon RH, Engelhardt JF, Yang Y, Zepeda M, Weber-Pendleton S, Grossman M, Wilson JM (1993) Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: toxicity study. Hum Gene Ther 4: 771–780

    Article  CAS  PubMed  Google Scholar 

  47. Joseph PM, O’Sullivan BP, Lapey A, Dorkin H, Oren J, Balfour R, Perricone MA, Rosenberg M, Wadsworth SC, Smith AE et al. (2001) Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. I. Methods, safety, and clinical implications. Hum Gene Ther 12: 1369–1382

    Article  CAS  PubMed  Google Scholar 

  48. Harvey BG, Maroni J, O’Donoghue KA, Chu KW, Muscat JC, Pippo AL, Wright CE, Hollmann C, Wisnivesky JP, Kessler PD et al. (2002) Safety of local delivery of low-and intermediate-dose adenovirus gene transfer vectors to individuals with a spectrum of morbid conditions. Hum Gene Ther 13: 15–63

    Article  CAS  PubMed  Google Scholar 

  49. Yang Y, Nunes FA, Berencsi K, Gonczol E, Engelhardt JF, Wilson JM (1994) Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis. Nat Genet 7: 362–369

    Article  CAS  PubMed  Google Scholar 

  50. Yang Y, Li Q, Ertl HC, Wilson JM (1995) Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol 69: 2004–2015

    CAS  PubMed  Google Scholar 

  51. Toietta G, Koehler DR, Finegold MJ, Lee B, Hu J, Beaudet AL (2003) Reduced inflammation and improved airway expression using helper-dependent adenoviral vectors with a K18 promoter. Mol Ther 7: 649–658

    Article  CAS  PubMed  Google Scholar 

  52. Koehler DR, Hannam V, Belcastro R, Steer B, Wen Y, Post M, Downey G, Tanswell AK, Hu J (2001) Targeting transgene expression for cystic fibrosis gene therapy. Mol Ther 4: 58–65

    Article  CAS  PubMed  Google Scholar 

  53. Koehler DR, Sajjan U, Chow YH, Martin B, Kent G, Tanswell AK, McKerlie C, Forstner JF, Hu J (2003) Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia. Proc Natl Acad Sci USA 100: 15364–15369

    Article  CAS  PubMed  Google Scholar 

  54. Koehler DR, Frndova H, Leung K, Louca E, Palmer D, Ng P, McKerlie C, Cox P, Coates AL, Hu J (2005) Aerosol delivery of an enhanced helper-dependent adenovirus formulation to rabbit lung using an intratracheal catheter. J Gene Med 7: 1409–1420

    Article  CAS  PubMed  Google Scholar 

  55. Hiatt P, Brunetti-Pierri N, Koehler D, McConnell R, Katkin J, Palmer DJ, Dimmock D, Hu J, Fine-Gold M, Beaudet AL et al. (2005) Aerosol delivery of helper-dependent adenoviral vector into nonhuman primate lungs results in high efficiency pulmonary transduction with minimal toxicity. Mol Ther 11: S317

    Article  Google Scholar 

  56. Hiatt P, Brunetti-Pierri N, McConnell R, Palmer D, Zuo Y, Finegold M, Beaudet A, Ng P (2007) Bronchoscope-guided, targeted lobar aerosolization of HDAd into nonhuman primate lungs results in uniform, high level pulmonary transduction, long term transgene expression and negligible toxicity. Mol Ther 15: S161

    Google Scholar 

  57. Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA et al. (2008) Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321: 1837–1841

    Article  CAS  PubMed  Google Scholar 

  58. Moss RB, Rodman D, Spencer LT, Aitken ML, Zeitlin PL, Waltz D, Milla C, Brody AS, Clancy JP, Ramsey B et al. (2004) Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 125: 509–521

    Article  PubMed  Google Scholar 

  59. Persson A, Fan X, Widegren B, Englund E (2006) Cell type-and region-dependent coxsackie adenovirus receptor expression in the central nervous system. J Neurooncol 78: 1–6

    Article  CAS  PubMed  Google Scholar 

  60. Le Gal La Salle G, Robert JJ, Berrard S, Ridoux V, Stratford-Perricaudet LD, Perricaudet M, Mallet J (1993) An adenovirus vector for gene transfer into neurons and glia in the brain. Science 259: 988–990

    Article  PubMed  Google Scholar 

  61. Davidson BL, Allen ED, Kozarsky KF, Wilson JM, Roessler BJ (1993) A model system for in vivo gene transfer into the central nervous system using an adenoviral vector. Nat Genet 3: 219–223

    Article  CAS  PubMed  Google Scholar 

  62. Byrnes AP, Wood MJ, Charlton HM (1996) Role of T cells in inflammation caused by adenovirus vectors in the brain. Gene Ther 3: 644–651

    CAS  PubMed  Google Scholar 

  63. Perry VH, Andersson PB, Gordon S (1993) Macrophages and inflammation in the central nervous system. Trends Neurosci 16: 268–273

    Article  CAS  PubMed  Google Scholar 

  64. Thomas CE, Schiedner G, Kochanek S, Castro MG, Lowenstein PR (2000) Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: toward realistic longterm neurological gene therapy for chronic diseases. Proc Natl Acad Sci USA 97: 7482–7487

    Article  CAS  PubMed  Google Scholar 

  65. Xiong W, Goverdhana S, Sciascia SA, Candolfi M, Zirger JM, Barcia C, Curtin JF, King GD, Jaita G, Liu C et al. (2006) Regulatable gutless adenovirus vectors sustain inducible transgene expression in the brain in the presence of an immune response against adenoviruses. J Virol 80: 27–37

    Article  CAS  PubMed  Google Scholar 

  66. Barcia C, Jimenez-Dalmaroni M, Kroeger KM, Puntel M, Rapaport AJ, Larocque D, King GD, Johnson SA, Liu C, Xiong W et al. (2007) One-year expression from high-capacity adenoviral vectors in the brains of animals with pre-existing anti-adenoviral immunity: clinical implications. Mol Ther 15: 2154–2163

    Article  CAS  PubMed  Google Scholar 

  67. Huang B, Schiefer J, Sass C, Landwehrmeyer GB, Kosinski CM, Kochanek S (2007) High-capacity adenoviral vector-mediated reduction of huntingtin aggregate load in vitro and in vivo. Hum Gene Ther 18: 303–311

    Article  CAS  PubMed  Google Scholar 

  68. Butti E, Bergami A, Recchia A, Brambilla E, Del Carro U, Amadio S, Cattalini A, Esposito M, Stornaiuolo A, Comi G et al. (2008) IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis. Gene Ther 15: 504–515

    Article  CAS  PubMed  Google Scholar 

  69. Butti E, Bergami A, Recchia A, Brambilla E, Franciotta D, Cattalini A, Stornaiuolo A, Lachapelle F, Comi G, Mavilio F et al. (2008) Absence of an intrathecal immune reaction to a helper-dependent adenoviral vector delivered into the cerebrospinal fluid of non-human primates. Gene Ther 15: 233–238

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 630E, Houston, TX, 77030, USA

    Nicola Brunetti-Pierri & Philip Ng

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  1. Nicola Brunetti-Pierri
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  1. Bone and Joint Research Unit Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Yuti Chernajovsky

  2. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Paul D. Robbins

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Brunetti-Pierri, N., Ng, P. (2010). Helper-dependent adenoviral vectors. In: Chernajovsky, Y., Robbins, P.D. (eds) Gene Therapy for Autoimmune and Inflammatory Diseases. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-0346-0165-8_13

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