Gene therapy with helper-dependent adenoviral vectors: Current advances and future perspectives

Viruses

Volumn 2, Issue 9, 2010, Pages 1886-1917

  Vetrini, Francesco ^a   Ng, Philip ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Helper dependent adenovirus; Innate and adaptive immune response; Liver transduction; Lung transduction

Indexed keywords

ADENOVIRUS VECTOR; ALPHA 1 ANTITRYPSIN; APOLIPOPROTEIN E; BETACELLULIN; BLOOD CLOTTING FACTOR 9; CYTOKERATIN 18; DYSTROPHIN; ERYTHROPOIETIN; FLT3 LIGAND; GLUCURONOSYLTRANSFERASE 1A1; HELPER DEPENDENT ADENOVIRUS VECTOR; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; HUNTINGTIN; NEUROGENIC DIFFERENTIATION FACTOR; PARVOVIRUS VECTOR; SHORT HAIRPIN RNA; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; THYMIDINE KINASE 1; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; VIRUS MESSENGER RNA;

ACUTE TOXICITY; ADAPTIVE IMMUNITY; ADENOVIRUS 5; AORTA ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CELL TRANSFER; CELLULAR IMMUNITY; CHRONIC KIDNEY DISEASE; CRIGLER NAJJAR SYNDROME; CYSTIC FIBROSIS; CYTOKINE RESPONSE; CYTOTOXICITY; DIABETES MELLITUS; DNA SEQUENCE; DRUG MECHANISM; DUCHENNE MUSCULAR DYSTROPHY; EARLY RESPONSE GENE; EX VIVO GENE TRANSFER; GENE LOCUS; GENE SILENCING; GENETIC CODE; GLIOBLASTOMA; HEMOPHILIA B; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMORAL IMMUNITY; HUNTINGTON CHOREA; IN VIVO GENE TRANSFER; LIVER STRUCTURE; LIVER TOXICITY; MOLECULAR INTERACTION; NONHUMAN; OBESITY; REPEAT PROCEDURE; RETINA DEGENERATION; REVIEW; SIDE EFFECT; TARGETED GENE REPAIR; THROMBOCYTOPENIA; TOXICITY TESTING; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; VIRION; VIRUS ASSEMBLY; VIRUS MORPHOLOGY; VIRUS RECOMBINANT; VIRUS REPLICATION;

ADENOVIRIDAE;

EID: 79952143411     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v2091886     Document Type: Review

References (159)

1. Paielli, D.L.; Wing, M.S.; Rogulski, K.R.; Gilbert, J.D.; Kolozsvary, A.; Kim, J.H.; Hughes, J.; Schnell, M.; Thompson, T.; Freytag, S.O. Evaluation of the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent human adenovirus following intraprostatic administration in the mouse. Mol. Ther. 2000, 1, 263-274.
2. Muruve, D.A.; Barnes, M.J.; Stillman, I.E.; Libermann, T.A. Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo. Hum. Gene Ther. 1999, 10, 965-976.
3. Muruve, D.A.; Cotter, M.J.; Zaiss, A.K.; White, L.R.; Liu, Q.; Chan, T.; Clark, S.A.; Ross, P.J.; Meulenbroek, R.A.; Maelandsmo, G.M.; Parks, R.J. Helper-dependent adenovirus vectors elicit intact innate but attenuated adaptive host immune responses in vivo. J. Virol. 2004, 78, 5966-5972.
4. Brunetti-Pierri, N.; Ng, P. Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors. Gene Ther. 2008, 15, 553-560.
5. Toietta, G.; Koehler, D.R.; Finegold, M.J.; Lee, B.; Hu, J.; Beaudet, A.L. Reduced inflammation and improved airway expression using helper-dependent adenoviral vectors with a K18 promoter. Mol. Ther. 2003, 7, 649-658.
6. Simonet, W.S.; Bucay, N.; Lauer, S.J.; Taylor, J.M. A far-downstream hepatocyte-specific control region directs expression of the linked human apolipoprotein E and C-I genes in transgenic mice. J. Biol. Chem. 1993, 268, 8221-8229.
7. Benihoud, K.; Yeh, P.; Perricaudet, M. Adenovirus vectors for gene delivery. Curr. Opin. Biotechnol. 1999, 10, 440-447.
8. Jozkowicz, A.; Dulak, J. Helper-dependent adenoviral vectors in experimental gene therapy. Acta Biochim. Pol. 2005, 52, 589-599.
9. Hong, S.S.; Karayan, L.; Tournier, J.; Curiel, D.T.; Boulanger, P.A. Adenovirus type 5 fiber knob binds to MHC class I alpha2 domain at the surface of human epithelial and B lymphoblastoid cells. EMBO J. 1997, 16, 2294-2306.
10. Tomko, R.P.; Xu, R.; Philipson, L. HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 3352-3356.
11. Tomko, R.P.; Johansson, C.B.; Totrov, M.; Abagyan, R.; Frisen, J.; Philipson, L. Expression of the adenovirus receptor and its interaction with the fiber knob. Exp. Cell Res. 2000, 255, 47-55.
12. Bergelson, J.M. Receptors mediating adenovirus attachment and internalization. Biochem. Pharmacol. 1999, 57, 975-979.
13. Wickham, T.J.; Mathias, P.; Cheresh, D.A.; Nemerow, G.R. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 1993, 73, 309-319.
14. Wickham, T.J.; Carrion, M.E.; Kovesdi, I. Targeting of adenovirus penton base to new receptors through replacement of its RGD motif with other receptor-specific peptide motifs. Gene Ther. 1995, 2, 750-756.
15. Wickham, T.J. Targeting adenovirus. Gene Ther. 2000, 7, 110-114.
16. Leopold, P.L.; Ferris, B.; Grinberg, I.; Worgall, S.; Hackett, N.R.; Crystal, R.G. Fluorescent virions: dynamic tracking of the pathway of adenoviral gene transfer vectors in living cells. Hum. Gene Ther. 1998, 9, 367-378.
17. Leopold, P.L.; Kreitzer, G.; Miyazawa, N.; Rempel, S.; Pfister, K.K.; Rodriguez-Boulan, E.; Crystal, R.G. Dynein- and microtubule-mediated translocation of adenovirus serotype 5 occurs after endosomal lysis. Hum. Gene Ther. 2000, 11, 151-165.
18. Greber, U.F.; Willetts, M.; Webster, P.; Helenius, A. Stepwise dismantling of adenovirus 2 during entry into cells. Cell 1993, 75, 477-486.
19. Ruben, M.; Bacchetti, S.; Graham, F. Covalently closed circles of adenovirus 5 DNA. Nature 1983, 301, 172-174.
20. Amalfitano, A.; Hauser, M.A.; Hu, H.; Serra, D.; Begy, C.R.; Chamberlain, J.S. Production and characterization of improved adenovirus vectors with the E1, E2b, and E3 genes deleted. J. Virol. 1998, 72, 926-933.
21. Imperiale, M.J.; Kao, H.T.; Feldman, L.T.; Nevins, J.R.; Strickland, S. Common control of the heat shock gene and early adenovirus genes: evidence for a cellular E1A-like activity. Mol. Cell Biol. 1984, 4, 867-874.
22. Reddy, P.S.; Sakhuja, K.; Ganesh, S.; Yang, L.; Kayda, D.; Brann, T.; Pattison, S.; Golightly, D.; Idamakanti, N.; Pinkstaff, A.; Kaloss, M.; Barjot, C.; Chamberlain, J.S.; Kaleko, M.; Connelly, S. Sustained human factor VIII expression in hemophilia A mice following systemic delivery of a gutless adenoviral vector. Mol. Ther. 2002, 5, 63-73.
23. Yang, Y.; Nunes, F.A.; Berencsi, K.; Gonczol, E.; Engelhardt, J.F.; Wilson, J.M. Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis. Nat. Genet. 1994, 7, 362-369.
24. Yang, Y.; Nunes, F.A.; Berencsi, K.; Furth, E.E.; Gonczol, E.; Wilson, J.M. Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 4407-4411.
25. Engelhardt, J.F.; Ye, X.; Doranz, B.; Wilson, J.M. Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 6196-6200.
26. Engelhardt, J.F.; Litzky, L.; Wilson, J.M. Prolonged transgene expression in cotton rat lung with recombinant adenoviruses defective in E2a. Hum. Gene Ther. 1994, 5, 1217-1229.
27. Fang, B.; Wang, H.; Gordon, G.; Bellinger, D.A.; Read, M.S.; Brinkhous, K.M.; Woo, S.L.; Eisensmith, R.C. Lack of persistence of E1- recombinant adenoviral vectors containing a temperature-sensitive E2A mutation in immunocompetent mice and hemophilia B dogs. Gene Ther. 1996, 3, 217-222.
28. Lusky, M.; Christ, M.; Rittner, K.; Dieterle, A.; Dreyer, D.; Mourot, B.; Schultz, H.; Stoeckel, F.; Pavirani, A.; Mehtali, M. In vitro and in vivo biology of recombinant adenovirus vectors with E1, E1/E2A, or E1/E4 deleted. J. Virol. 1998, 72, 2022-2032.
29. O'Neal, W.K.; Zhou, H.; Morral, N.; guilar-Cordova, E.; Pestaner, J.; Langston, C.; Mull, B.; Wang, Y.; Beaudet, A.L.; Lee, B. Toxicological comparison of E2a-deleted and first-generation adenoviral vectors expressing alpha1-antitrypsin after systemic delivery. Hum. Gene Ther. 1998, 9, 1587-1598.
30. Parks, R.J.; Chen, L.; Anton, M.; Sankar, U.; Rudnicki, M.A.; Graham, F.L. A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc. Natl. Acad. Sci. U. S. A. 1996, 93, 13565-13570.
31. Parks, R.J.; Graham, F.L. A helper-dependent system for adenovirus vector production helps define a lower limit for efficient DNA packaging. J. Virol. 1997, 71, 3293-3298.
32. Parks, R.J.; Bramson, J.L.; Wan, Y.; Addison, C.L.; Graham, F.L. Effects of stuffer DNA on transgene expression from helper-dependent adenovirus vectors. J. Virol. 1999, 73, 8027-8034.
33. Palmer, D.; Ng, P. Improved system for helper-dependent adenoviral vector production. Mol. Ther. 2003, 8, 846-852.
34. Brunetti-Pierri, N.; Palmer, D.J.; Beaudet, A.L.; Carey, K.D.; Finegold, M.; Ng, P. Acute toxicity after high-dose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Hum. Gene Ther. 2004, 15, 35-46.
35. Brunetti-Pierri, N.; Nichols, T.C.; McCorquodale, S.; Merricks, E.; Palmer, D.J.; Beaudet, A.L.; Ng, P. Sustained phenotypic correction of canine hemophilia B after systemic administration of helper-dependent adenoviral vector. Hum. Gene Ther. 2005, 16, 811-820.
36. Brunetti-Pierri, N.; Ng, T.; Iannitti, D.A.; Palmer, D.J.; Beaudet, A.L.; Finegold, M.J.; Carey, K.D.; Cioffi, W.G.; Ng, P. Improved hepatic transduction, reduced systemic vector dissemination, and long-term transgene expression by delivering helper-dependent adenoviral vectors into the surgically isolated liver of nonhuman primates. Hum. Gene Ther. 2006, 17, 391-404.
37. Brunetti-Pierri, N.; Stapleton, G.E.; Palmer, D.J.; Zuo, Y.; Mane, V.P.; Finegold, M.J.; Beaudet, A.L.; Leland, M.M.; Mullins, C.E.; Ng, P. Pseudo-hydrodynamic delivery of helper-dependent adenoviral vectors into non-human primates for liver-directed gene therapy. Mol. Ther. 2007, 15, 732-740.
38. Brunetti-Pierri, N.; Stapleton, G.E.; Law, M.; Breinholt, J.; Palmer, D.J.; Zuo, Y.; Grove, N.C.; Finegold, M.J.; Rice, K.; Beaudet, A.L.; Mullins, C.E.; Ng, P. Efficient, long-term hepatic gene transfer using clinically relevant HDAd doses by balloon occlusion catheter delivery in nonhuman primates. Mol. Ther. 2009, 17, 327-333.
39. McCormack, W.M.Jr.; Seiler, M.P.; Bertin, T.K.; Ubhayakar, K.; Palmer, D.J.; Ng, P.; Nichols, T.C.; Lee, B. Helper-dependent adenoviral gene therapy mediates long-term correction of the clotting defect in the canine hemophilia A model. J. Thromb. Haemost. 2006, 4, 1218-1225.
40. Ng, P.; Beauchamp, C.; Evelegh, C.; Parks, R.; Graham, F.L. Development of a FLP/frt system for generating helper-dependent adenoviral vectors. Mol. Ther. 2001, 3, 809-815.
41. Umana, P.; Gerdes, C.A.; Stone, D.; Davis, J.R.; Ward, D.; Castro, M.G.; Lowenstein, P.R. Efficient FLPe recombinase enables scalable production of helper-dependent adenoviral vectors with negligible helper-virus contamination. Nat. Biotechnol. 2001, 19, 582-585.
42. Ehrhardt, A.; Xu, H.; Kay, M.A. Episomal persistence of recombinant adenoviral vector genomes during the cell cycle in vivo. J. Virol. 2003, 77, 7689-7695.
43. Jager, L.; Ehrhardt, A. Persistence of high-capacity adenoviral vectors as replication-defective monomeric genomes in vitro and in murine liver. Hum. Gene Ther. 2009, 20, 883-896.
44. Kennedy, M.A.; Parks, R.J. Adenovirus virion stability and the viral genome: size matters. Mol. Ther. 2009, 17, 1664-1666.
45. Schiedner, G.; Hertel, S.; Johnston, M.; Biermann, V.; Dries, V.; Kochanek, S. Variables affecting in vivo performance of high-capacity adenovirus vectors. J. Virol. 2002, 76, 1600-1609.
46. Soifer, H.; Higo, C.; Kazazian, H.H., Jr.; Moran, J.V.; Mitani, K.; Kasahara, N. Stable integration of transgenes delivered by a retrotransposon-adenovirus hybrid vector. Hum. Gene Ther. 2001, 12, 1417-1428.
47. Kim, I.H.; Jozkowicz, A.; Piedra, P.A.; Oka, K.; Chan, L. Lifetime correction of genetic deficiency in mice with a single injection of helper-dependent adenoviral vector. Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 13282-13287.
48. Palinski, W.; Ord, V.A.; Plump, A.S.; Breslow, J.L.; Steinberg, D.; Witztum, J.L. ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. Arterioscler. Thromb. 1994, 14, 605-616.
49. Strauss, K.A.; Robinson, D.L.; Vreman, H.J.; Puffenberger, E.G.; Hart, G.; Morton, D.H. Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease. Eur. J. Pediatr. 2006, 165, 306-319.
50. Toietta, G.; Mane, V.P.; Norona, W.S.; Finegold, M.J.; Ng, P.; McDonagh, A.F.; Beaudet, A.L.; Lee, B. Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 3930-3935.
51. Kojima, H.; Fujimiya, M.; Matsumura, K.; Younan, P.; Imaeda, H.; Maeda, M.; Chan, L. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat. Med. 2003, 9, 596-603.
52. Witting, S.R.; Brown, M.; Saxena, R.; Nabinger, S.; Morral, N. Helper-dependent adenovirus-mediated short hairpin RNA expression in the liver activates the interferon response. J. Biol. Chem. 2008, 283, 2120-2128.
53. Ruiz, R.; Witting, S.R.; Saxena, R.; Morral, N. Robust hepatic gene silencing for functional studies using helper-dependent adenovirus vectors. Hum. Gene Ther. 2008.
54. Grimm, D.; Streetz, K.L.; Jopling, C.L.; Storm, T.A.; Pandey, K.; Davis, C.R.; Marion, P.; Salazar, F.; Kay, M.A. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 2006, 441, 537-541.
55. Brown, B.D.; Shi, C.X.; Powell, S.; Hurlbut, D.; Graham, F.L.; Lillicrap, D. Helper-dependent adenoviral vectors mediate therapeutic factor VIII expression for several months with minimal accompanying toxicity in a canine model of severe hemophilia A. Blood 2004, 103, 804-810.
56. Morral, N.; O'Neal, W.; Rice, K.; Leland, M.; Kaplan, J.; Piedra, P.A.; Zhou, H.; Parks, R.J.; Velji, R.; guilar-Cordova, E.; Wadsworth, S.; Graham, F.L.; Kochanek, S.; Carey, K.D.; Beaudet, A.L. 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. U. S. A. 1999, 96, 12816-12821.
57. Di Paolo, N.C.; Van, R.N.; Shayakhmetov, D.M. Redundant and synergistic mechanisms control the sequestration of blood-born adenovirus in the liver. Mol. Ther. 2009, 17, 675-684.
58. Xu, Z.; Tian, J.; Smith, J.S.; Byrnes, A.P. Clearance of adenovirus by Kupffer cells is mediated by scavenger receptors, natural antibodies, and complement. J. Virol. 2008, 82, 11705-11713.
59. Parker, A.L.; Waddington, S.N.; Nicol, C.G.; Shayakhmetov, D.M.; Buckley, S.M.; Denby, L.; Kemball-Cook, G.; Ni, S.; Lieber, A.; McVey, J.H.; Nicklin, S.A.; Baker, A.H. Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. Blood 2006, 108, 2554-2561.
60. Parker, A.L.; McVey, J.H.; Doctor, J.H.; Lopez-Franco, O.; Waddington, S.N.; Havenga, M.J.; Nicklin, S.A.; Baker, A.H. Influence of coagulation factor zymogens on the infectivity of adenoviruses pseudotyped with fibers from subgroup D. J. Virol. 2007, 81, 3627-3631.
61. Shayakhmetov, D.M.; Gaggar, A.; Ni, S.; Li, Z.Y.; Lieber, A. Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity. J. Virol. 2005, 79, 7478-7491.
62. Waddington, S.N.; Parker, A.L.; Havenga, M.; Nicklin, S.A.; Buckley, S.M.; McVey, J.H.; Baker, A.H. Targeting of adenovirus serotype 5 (Ad5) and 5/47 pseudotyped vectors in vivo: fundamental involvement of coagulation factors and redundancy of CAR binding by Ad5. J. Virol. 2007, 81, 9568-9571.
63. Waddington, S.N.; McVey, J.H.; Bhella, D.; Parker, A.L.; Barker, K.; Atoda, H.; Pink, R.; Buckley, S.M.; Greig, J.A.; Denby, L.; Custers, J.; Morita, T.; Francischetti, I.M.; Monteiro, R.Q.; Barouch, D.H.; Van, R.N.; Napoli, C.; Havenga, M.J.; Nicklin, S.A.; Baker, A.H. Adenovirus serotype 5 hexon mediates liver gene transfer. Cell 2008, 132, 397-409.
64. Alba, R.; Bradshaw, A.C.; Parker, A.L.; Bhella, D.; Waddington, S.N.; Nicklin, S.A.; Van, R.N.; Custers, J.; Goudsmit, J.; Barouch, D.H.; McVey, J.H.; Baker, A.H. Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer. Blood 2009, 114, 965-971.
65. Sakurai, F.; Mizuguchi, H.; Yamaguchi, T.; Hayakawa, T. Characterization of in vitro and in vivo gene transfer properties of adenovirus serotype 35 vector. Mol. Ther. 2003, 8, 813-821.
66. Tao, N.; Gao, G.P.; Parr, M.; Johnston, J.; Baradet, T.; Wilson, J.M.; Barsoum, J.; Fawell, S.E. Sequestration of adenoviral vector by Kupffer cells leads to a nonlinear dose response of transduction in liver. Mol. Ther. 2001, 3, 28-35.
67. Yu, Q.; Que, L.G.; Rockey, D.C. Adenovirus-mediated gene transfer to nonparenchymal cells in normal and injured liver. Am. J. Physiol. Gastrointest. Liver Physiol. 2002, 282, G565-G572.
68. Tian, J.; Xu, Z.; Smith, J.S.; Hofherr, S.E.; Barry, M.A.; Byrnes, A.P. Adenovirus activates complement by distinctly different mechanisms in vitro and in vivo: indirect complement activation by virions in vivo. J. Virol. 2009, 83, 5648-5658.
69. Stone, D.; Liu, Y.; Shayakhmetov, D.; Li, Z.Y.; Ni, S.; Lieber, A. Adenovirus-platelet interaction in blood causes virus sequestration to the reticuloendothelial system of the liver. J. Virol. 2007, 81, 4866-4871.
70. Schiedner, G.; Hertel, S.; Johnston, M.; Dries, V.; Van, R.N.; Kochanek, S. Selective depletion or blockade of Kupffer cells leads to enhanced and prolonged hepatic transgene expression using high-capacity adenoviral vectors. Mol. Ther. 2003, 7, 35-43.
71. Morral, N.; O'Neal, W.K.; Rice, K.; Leland, M.M.; Piedra, P.A.; guilar-Cordova, E.; Carey, K.D.; Beaudet, A.L.; Langston, C. Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. Hum. Gene Ther. 2002, 13, 143-154.
72. Bowen, G.P.; Borgland, S.L.; Lam, M.; Libermann, T.A.; Wong, N.C.; Muruve, D.A. Adenovirus vector-induced inflammation: capsid-dependent induction of the C-C chemokine RANTES requires NF-kappa B. Hum. Gene Ther. 2002, 13, 367-379.
73. Zhu, J.; Huang, X.; Yang, Y. Innate immune response to adenoviral vectors is mediated by both Toll-like receptor-dependent and -independent pathways. J. Virol. 2007, 81, 3170-3180.
74. Appledorn, D.M.; Patial, S.; McBride, A.; Godbehere, S.; Van, R.N.; Parameswaran, N.; Amalfitano, A. Adenovirus vector-induced innate inflammatory mediators, MAPK signaling, as well as adaptive immune responses are dependent upon both TLR2 and TLR9 in vivo. J. Immunol. 2008, 181, 2134-2144.
75. Appledorn, D.M.; Patial, S.; Godbehere, S.; Parameswaran, N.; Amalfitano, A. TRIF, and TRIF-interacting TLRs differentially modulate several adenovirus vector-induced immune responses. J. Innate. Immun. 2009, 1, 376-388.
76. Cerullo, V.; Seiler, M.P.; Mane, V.; Brunetti-Pierri, N.; Clarke, C.; Bertin, T.K.; Rodgers, J.R.; Lee, B. Toll-like receptor 9 triggers an innate immune response to helper-dependent adenoviral vectors. Mol. Ther. 2007, 15, 378-385.
77. Hartman, Z.C.; Black, E.P.; Amalfitano, A. Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells. Virology 2007, 358, 357-372.
78. Hartman, Z.C.; Kiang, A.; Everett, R.S.; Serra, D.; Yang, X.Y.; Clay, T.M.; Amalfitano, A. Adenovirus infection triggers a rapid, MyD88-regulated transcriptome response critical to acute-phase and adaptive immune responses in vivo. J. Virol. 2007, 81, 1796-1812.
79. Zhu, J.; Huang, X.; Yang, Y. Type I IFN signaling on both B and CD4 T cells is required for protective antibody response to adenovirus. J. Immunol. 2007, 178, 3505-3510.
80. Zhu, J.; Huang, X.; Yang, Y. A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo. Mol. Ther. 2008, 16, 1300-1307.
81. Nayak, S.; Herzog, R.W. Progress and prospects: immune responses to viral vectors. Gene Ther. 2010, 17, 295-304.
82. Nociari, M.; Ocheretina, O.; Schoggins, J.W.; Falck-Pedersen, E. Sensing infection by adenovirus: Toll-like receptor-independent viral DNA recognition signals activation of the interferon regulatory factor 3 master regulator. J. Virol. 2007, 81, 4145-4157.
83. Di Paolo, N.C.; Miao, E.A.; Iwakura, Y.; Murali-Krishna, K.; Aderem, A.; Flavell, R.A.; Papayannopoulou, T.; Shayakhmetov, D.M. Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity 2009, 31, 110-121.
84. Cichon, G.; Boeckh-Herwig, S.; Schmidt, H.H.; Wehnes, E.; Muller, T.; Pring-Akerblom, P.; Burger, R. Complement activation by recombinant adenoviruses. Gene Ther. 2001, 8, 1794-1800.
85. Kiang, A.; Hartman, Z.C.; Everett, R.S.; Serra, D.; Jiang, H.; Frank, M.M.; Amalfitano, A. Multiple innate inflammatory responses induced after systemic adenovirus vector delivery depend on a functional complement system. Mol. Ther. 2006, 14, 588-598.
86. Othman, M.; Labelle, A.; Mazzetti, I.; Elbatarny, H.S.; Lillicrap, D. Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance. Blood 2007, 109, 2832-2839.
87. Harding, T.C.; Koprivnikar, K.E.; Tu, G.H.; Zayek, N.; Lew, S.; Subramanian, A.; Sivakumaran, A.; Frey, D.; Ho, K.; VanRoey, M.J.; Nichols, T.C.; Bellinger, D.A.; Yendluri, S.; Waugh, J.; McArthur, J.; Veres, G.; Donahue, B.A. Intravenous administration of an AAV-2 vector for the expression of factor IX in mice and a dog model of hemophilia B. Gene Ther. 2004, 11, 204-213.
88. Chao, H.; Liu, Y.; Rabinowitz, J.; Li, C.; Samulski, R.J.; Walsh, C.E. Several log increase in therapeutic transgene delivery by distinct adeno-associated viral serotype vectors. Mol. Ther. 2000, 2, 619-623.
89. Cordier, L.; Hack, A.A.; Scott, M.O.; Barton-Davis, E.R.; Gao, G.; Wilson, J.M.; McNally, E.M.; Sweeney, H.L. Rescue of skeletal muscles of gamma-sarcoglycan-deficient mice with adeno-associated virus-mediated gene transfer. Mol. Ther. 2000, 1, 119-129.
90. Dinculescu, A.; Glushakova, L.; Min, S.H.; Hauswirth, W.W. Adeno-associated virus-vectored gene therapy for retinal disease. Hum. Gene Ther. 2005, 16, 649-663.
91. Zaiss, A.K.; Muruve, D.A. Immunity to adeno-associated virus vectors in animals and humans: a continued challenge. Gene Ther. 2008, 15, 808-816.
92. Mingozzi, F.; Maus, M.V.; Hui, D.J.; Sabatino, D.E.; Murphy, S.L.; Rasko, J.E.; Ragni, M.V.; Manno, C.S.; Sommer, J.; Jiang, H.; Pierce, G.F.; Ertl, H.C.; High, K.A. CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat. Med. 2007, 13, 419-422.
93. Pien, G.C.; Basner-Tschakarjan, E.; Hui, D.J.; Mentlik, A.N.; Finn, J.D.; Hasbrouck, N.C.; Zhou, S.; Murphy, S.L.; Maus, M.V.; Mingozzi, F.; Orange, J.S.; High, K.A. Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors. J. Clin. Invest 2009, 119, 1688-1695.
94. Roth, M.D.; Cheng, Q.; Harui, A.; Basak, S.K.; Mitani, K.; Low, T.A.; Kiertscher, S.M. Helper-dependent adenoviral vectors efficiently express transgenes in human dendritic cells but still stimulate antiviral immune responses. J. Immunol. 2002, 169, 4651-4656.
95. Kafri, T.; Morgan, D.; Krahl, T.; Sarvetnick, N.; Sherman, L.; Verma, I. Cellular immune response to adenoviral vector infected cells does not require de novo viral gene expression: implications for gene therapy. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 11377-11382.
96. Kushwah, R.; Cao, H.; Hu, J. Potential of helper-dependent adenoviral vectors in modulating airway innate immunity. Cell Mol. Immunol. 2007, 4, 81-89.
97. Kushwah, R.; Cao, H.; Hu, J. Characterization of pulmonary T cell response to helper-dependent adenoviral vectors following intranasal delivery. J. Immunol. 2008, 180, 4098-4108.
98. Jacobs, F.; Feng, Y.; Van, C.E.; Lievens, J.; Snoeys, J.; De, G.B. Species differences in hepatocyte-directed gene transfer: implications for clinical translation. Curr. Gene Ther. 2009, 9, 83-90.
99. Jacobs, F.; Wisse, E.; De, G.B. The role of liver sinusoidal cells in hepatocyte-directed gene transfer. Am. J. Pathol. 2010, 176, 14-21.
100. Vetrini, F.; Brunetti-Pierri, N.; Palmer, D.J.; Bertin, T.; Grove, N.C.; Finegold, M.J.; Ng, P. Vasoactive Intestinal Peptide Increases Hepatic Transduction and Reduces Innate Immune Response Following Administration of Helper-dependent Ad. Mol. Ther. 2010.
101. Ajuf'ev, B.N.; Dizhe, E.B.; Efremov, A.M.; Mogilenko, D.A.; Oleinikova, G.N.; Lapikov, I.A.; Zhdanova, O.I.; Kidgotko, O.V.; Orlov, S.V.; Perevozchikov, A.P. [Hydrodynamics-based transfer of human apolipoprotein A-I gene into mice: study of factors involving an efficacy and duration of the transferred gene expression in animals' liver]. Mol. Biol. (Mosk) 2004, 38, 1076-1084.
102. Brunetti-Pierri, N.; Palmer, D.J.; Mane, V.; Finegold, M.; Beaudet, A.L.; Ng, P. Increased hepatic transduction with reduced systemic dissemination and proinflammatory cytokines following hydrodynamic injection of helper-dependent adenoviral vectors. Mol. Ther. 2005, 12, 99-106.
103. Wolff, L.J.; Wolff, J.A.; Sebestyen, M.G. Effect of tissue-specific promoters and microRNA recognition elements on stability of transgene expression after hydrodynamic naked plasmid DNA delivery. Hum. Gene Ther. 2009, 20, 374-388.
104. Yotnda, P.; Chen, D.H.; Chiu, W.; Piedra, P.A.; Davis, A.; Templeton, N.S.; Brenner, M.K. Bilamellar cationic liposomes protect adenovectors from preexisting humoral immune responses. Mol. Ther. 2002, 5, 233-241.
105. Croyle, M.A.; Chirmule, N.; Zhang, Y.; Wilson, J.M. PEGylation of E1-deleted adenovirus vectors allows significant gene expression on readministration to liver. Hum. Gene Ther. 2002, 13, 1887-1900.
106. Hofherr, S.E.; Mok, H.; Gushiken, F.C.; Lopez, J.A.; Barry, M.A. Polyethylene glycol modification of adenovirus reduces platelet activation, endothelial cell activation, and thrombocytopenia. Hum. Gene Ther. 2007, 18, 837-848.
107. Mok, H.; Palmer, D.J.; Ng, P.; Barry, M.A. Evaluation of polyethylene glycol modification of first-generation and helper-dependent adenoviral vectors to reduce innate immune responses. Mol. Ther. 2005, 11, 66-79.
108. De, G.B.; Snoeys, J.; Van, L.S.; Lievens, J.; Collen, D. Elimination of innate immune responses and liver inflammation by PEGylation of adenoviral vectors and methylprednisolone. Hum. Gene Ther. 2005, 16, 1439-1451.
109. Seregin, S.S.; Appledorn, D.M.; McBride, A.J.; Schuldt, N.J.; Aldhamen, Y.A.; Voss, T.; Wei, J.; Bujold, M.; Nance, W.; Godbehere, S.; Amalfitano, A. Transient pretreatment with glucocorticoid ablates innate toxicity of systemically delivered adenoviral vectors without reducing efficacy. Mol. Ther. 2009, 17, 685-696.
110. Culling, B.; Ogle, R. Genetic counselling issues in cystic fibrosis. Paediatr. Respir. Rev. 2010, 11, 75-79.
111. O'Riordan, S.M.; Dattani, M.T.; Hindmarsh, P.C. Cystic fibrosis-related diabetes in childhood. Horm. Res. Paediatr. 2010, 73, 15-24.
112. Pickles, R.J.; McCarty, D.; Matsui, H.; Hart, P.J.; Randell, S.H.; Boucher, R.C. Limited entry of adenovirus vectors into well-differentiated airway epithelium is responsible for inefficient gene transfer. J. Virol. 1998, 72, 6014-6023.
113. Pickles, R.J.; Fahrner, J.A.; Petrella, J.M.; Boucher, R.C.; Bergelson, J.M. Retargeting the coxsackievirus and adenovirus receptor to the apical surface of polarized epithelial cells reveals the glycocalyx as a barrier to adenovirus-mediated gene transfer. J. Virol. 2000, 74, 6050-6057.
114. Engelhardt, J.F.; Simon, R.H.; Yang, Y.; Zepeda, M.; Weber-Pendleton, S.; Doranz, B.; Grossman, M.; Wilson, J.M. Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: biological efficacy study. Hum. Gene Ther. 1993, 4, 759-769.
115. Engelhardt, J.F.; Yang, Y.; Stratford-Perricaudet, L.D.; Allen, E.D.; Kozarsky, K.; Perricaudet, M.; Yankaskas, J.R.; Wilson, J.M. Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1-deleted adenoviruses. Nat. Genet. 1993, 4, 27-34.
116. Simon, R.H.; Engelhardt, J.F.; Yang, Y.; Zepeda, M.; Weber-Pendleton, S.; Grossman, M.; Wilson, J.M. Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: toxicity study. Hum. Gene Ther. 1993, 4, 771-780.
117. Zuckerman, J.B.; Robinson, C.B.; McCoy, K.S.; Shell, R.; Sferra, T.J.; Chirmule, N.; Magosin, S.A.; Propert, K.J.; Brown-Parr, E.C.; Hughes, J.V.; Tazelaar, J.; Baker, C.; Goldman, M.J.; Wilson, J.M. A phase I study of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator gene to a lung segment of individuals with cystic fibrosis. Hum. Gene Ther. 1999, 10, 2973-2985.
118. Chu, Q.; St, G.J.; Lukason, M.; Cheng, S.H.; Scheule, R.K.; Eastman, S.J. EGTA enhancement of adenovirus-mediated gene transfer to mouse tracheal epithelium in vivo. Hum. Gene Ther. 2001, 12, 455-467.
119. Kaplan, J.M.; Pennington, S.E.; St George, J.A.; Woodworth, L.A.; Fasbender, A.; Marshall, J.; Cheng, S.H.; Wadsworth, S.C.; Gregory, R.J.; Smith, A.E. Potentiation of gene transfer to the mouse lung by complexes of adenovirus vector and polycations improves therapeutic potential. Hum. Gene Ther. 1998, 9, 1469-1479.
120. Wang, G.; Zabner, J.; Deering, C.; Launspach, J.; Shao, J.; Bodner, M.; Jolly, D.J.; Davidson, B.L.; McCray, P.B., Jr. Increasing epithelial junction permeability enhances gene transfer to airway epithelia In vivo. Am. J. Respir. Cell Mol. Biol. 2000, 22, 129-138.
121. Chirmule, N.; Hughes, J.V.; Gao, G.P.; Raper, S.E.; Wilson, J.M. Role of E4 in eliciting CD4 T-cell and B-cell responses to adenovirus vectors delivered to murine and nonhuman primate lungs. J. Virol. 1998, 72, 6138-6145.
122. Goldman, M.J.; Litzky, L.A.; Engelhardt, J.F.; Wilson, J.M. Transfer of the CFTR gene to the lung of nonhuman primates with E1-deleted, E2a-defective recombinant adenoviruses: a preclinical toxicology study. Hum. Gene Ther. 1995, 6, 839-851.
123. Koehler, D.R.; Sajjan, U.; Chow, Y.H.; Martin, B.; Kent, G.; Tanswell, A.K.; McKerlie, C.; Forstner, J.F.; Hu, J. Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 15364-15369.
124. Koehler, D.R.; Frndova, H.; Leung, K.; Louca, E.; Palmer, D.; Ng, P.; McKerlie, C.; Cox, P.; Coates, A.L.; Hu, J. Aerosol delivery of an enhanced helper-dependent adenovirus formulation to rabbit lung using an intratracheal catheter. J. Gene Med. 2005, 7, 1409-1420.
125. Brunetti-Pierri, N.; Ng, P. Progress towards liver and lung-directed gene therapy with helper-dependent adenoviral vectors. Curr. Gene Ther. 2009, 9, 329-340.
126. Brown, J.; Mellis, C.M.; Wood, R.E. Edetate sodium aerosol in Pseudomonas lung infection in cystic fibrosis. Am. J. Dis. Child 1985, 139, 836-839.
127. Rogers, C.S.; Stoltz, D.A.; Meyerholz, D.K.; Ostedgaard, L.S.; Rokhlina, T.; Taft, P.J.; Rogan, M.P.; Pezzulo, A.A.; Karp, P.H.; Itani, O.A.; Kabel, A.C.; Wohlford-Lenane, C.L.; Davis, G.J.; Hanfland, R.A.; Smith, T.L.; Samuel, M.; Wax, D.; Murphy, C.N.; Rieke, A.; Whitworth, K.; Uc, A.; Starner, T.D.; Brogden, K.A.; Shilyansky, J.; McCray, P.B., Jr.; Zabner, J.; Prather, R.S.; Welsh, M.J. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 2008, 321, 1837-1841.
128. Moss, R.B.; Rodman, D.; Spencer, L.T.; Aitken, M.L.; Zeitlin, P.L.; Waltz, D.; Milla, C.; Brody, A.S.; Clancy, J.P.; Ramsey, B.; Hamblett, N.; Heald, A.E. 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 2004, 125, 509-521.
129. Johnson, L.G.; Olsen, J.C.; Sarkadi, B.; Moore, K.L.; Swanstrom, R.; Boucher, R.C. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat. Genet. 1992, 2, 21-25.
130. Segura, M.M.; Alba, R.; Bosch, A.; Chillon, M. Advances in helper-dependent adenoviral vector research. Curr. Gene Ther. 2008, 8, 222-235.
131. Dudley, R.W.; Lu, Y.; Gilbert, R.; Matecki, S.; Nalbantoglu, J.; Petrof, B.J.; Karpati, G. Sustained improvement of muscle function one year after full-length dystrophin gene transfer into mdx mice by a gutted helper-dependent adenoviral vector. Hum. Gene Ther. 2004, 15, 145-156.
132. Gilbert, R.; Nalbantoglu, J.; Howell, J.M.; Davies, L.; Fletcher, S.; Amalfitano, A.; Petrof, B.J.; Kamen, A.; Massie, B.; Karpati, G. Dystrophin expression in muscle following gene transfer with a fully deleted (gutted) adenovirus is markedly improved by trans-acting adenoviral gene products. Hum. Gene Ther. 2001, 12, 1741-1755.
133. Jiang, Z.; Feingold, E.; Kochanek, S.; Clemens, P.R. Systemic delivery of a high-capacity adenoviral vector expressing mouse CTLA4Ig improves skeletal muscle gene therapy. Mol. Ther. 2002, 6, 369-376.
134. Jiang, Z.; Schiedner, G.; Van, R.N.; Liu, C.C.; Kochanek, S.; Clemens, P.R. Sustained muscle expression of dystrophin from a high-capacity adenoviral vector with systemic gene transfer of T cell costimulatory blockade. Mol. Ther. 2004, 10, 688-696.
135. Bilbao, R.; Reay, D.P.; Hughes, T.; Biermann, V.; Volpers, C.; Goldberg, L.; Bergelson, J.; Kochanek, S.; Clemens, P.R. Fetal muscle gene transfer is not enhanced by an RGD capsid modification to high-capacity adenoviral vectors. Gene Ther. 2003, 10, 1821-1829.
136. Smith, P.E.; Calverley, P.M.; Edwards, R.H.; Evans, G.A.; Campbell, E.J. Practical problems in the respiratory care of patients with muscular dystrophy. N. Engl. J. Med. 1987, 316, 1197-1205.
137. Smith, P.E.; Calverley, P.M.; Edwards, R.H. Hypoxemia during sleep in Duchenne muscular dystrophy. Am. Rev. Respir. Dis. 1988, 137, 884-888.
138. Matecki, S.; Dudley, R.W.; Divangahi, M.; Gilbert, R.; Nalbantoglu, J.; Karpati, G.; Petrof, B.J. Therapeutic gene transfer to dystrophic diaphragm by an adenoviral vector deleted of all viral genes. Am. J. Physiol Lung Cell Mol. Physiol 2004, 287, L569-L576.
139. Maione, D.; Della, R.C.; Giannetti, P.; D'Arrigo, R.; Liberatoscioli, L.; Franlin, L.L.; Sandig, V.; Ciliberto, G.; La, M.N.; Savino, R. An improved helper-dependent adenoviral vector allows persistent gene expression after intramuscular delivery and overcomes preexisting immunity to adenovirus. Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 5986-5991.
140. Bramson, J.L.; Grinshtein, N.; Meulenbroek, R.A.; Lunde, J.; Kottachchi, D.; Lorimer, I.A.; Jasmin, B.J.; Parks, R.J. Helper-dependent adenoviral vectors containing modified fiber for improved transduction of developing and mature muscle cells. Hum. Gene Ther. 2004, 15, 179-188.
141. Persson, A.; Fan, X.; Widegren, B.; Englund, E. Cell type- and region-dependent coxsackie adenovirus receptor expression in the central nervous system. J. Neurooncol. 2006, 78, 1-6.
142. Davidson, B.L.; Allen, E.D.; Kozarsky, K.F.; Wilson, J.M.; Roessler, B.J. A model system for in vivo gene transfer into the central nervous system using an adenoviral vector. Nat. Genet. 1993, 3, 219-223.
143. Doran, S.E.; Roessler, B.J.; Hartman, J.W.; Hoff, J.T.; Shewach, D.S.; Davidson, B.L. Adenovirus-mediated in vivo gene transfer into the central nervous system of a nonhuman primate (resident award paper). Clin. Neurosurg. 1994, 41, 242-257.
144. Doran, S.E.; Ren, X.D.; Betz, A.L.; Pagel, M.A.; Neuwelt, E.A.; Roessler, B.J.; Davidson, B.L. Gene expression from recombinant viral vectors in the central nervous system after blood-brain barrier disruption. Neurosurgery 1995, 36, 965-970.
145. Byrnes, A.P.; Wood, M.J.; Charlton, H.M. Role of T cells in inflammation caused by adenovirus vectors in the brain. Gene Ther. 1996, 3, 644-651.
146. Byrnes, A.P.; MacLaren, R.E.; Charlton, H.M. Immunological instability of persistent adenovirus vectors in the brain: peripheral exposure to vector leads to renewed inflammation, reduced gene expression, and demyelination. J. Neurosci. 1996, 16, 3045-3055.
147. Thomas, C.E.; Schiedner, G.; Kochanek, S.; Castro, M.G.; Lowenstein, P.R. 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 long-term neurological gene therapy for chronic diseases. Proc. Natl. Acad. Sci. U. S. A. 2000, 97, 7482-7487.
148. Zou, L.; Yuan, X.; Zhou, H.; Lu, H.; Yang, K. Helper-dependent adenoviral vector-mediated gene transfer in aged rat brain. Hum. Gene Ther. 2001, 12, 181-191.
149. Butti, E.; Bergami, A.; Recchia, A.; Brambilla, E.; Franciotta, D.; Cattalini, A.; Stornaiuolo, A.; Lachapelle, F.; Comi, G.; Mavilio, F.; Martino, G.; Furlan, R. Absence of an intrathecal immune reaction to a helper-dependent adenoviral vector delivered into the cerebrospinal fluid of non-human primates. Gene Ther. 2008, 15, 233-238.
150. Butti, E.; Bergami, A.; Recchia, A.; Brambilla, E.; Del, C.U.; Amadio, S.; Cattalini, A.; Esposito, M.; Stornaiuolo, A.; Comi, G.; Pluchino, S.; Mavilio, F.; Martino, G.; Furlan, R. IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis. Gene Ther. 2008, 15, 504-515.
151. Huang, B.; Schiefer, J.; Sass, C.; Landwehrmeyer, G.B.; Kosinski, C.M.; Kochanek, S. High-capacity adenoviral vector-mediated reduction of huntingtin aggregate load in vitro and in vivo. Hum. Gene Ther. 2007, 18, 303-311.
152. Huang, B.; Schiefer, J.; Sass, C.; Kosinski, C.M.; Kochanek, S. Inducing huntingtin inclusion formation in primary neuronal cell culture and in vivo by high-capacity adenoviral vectors expressing truncated and full-length huntingtin with polyglutamine expansion. J. Gene Med. 2008, 10, 269-279.
153. Muhammad, A.K.; Puntel, M.; Candolfi, M.; Salem, A.; Yagiz, K.; Farrokhi, C.; Kroeger, K.M.; Xiong, W.; Curtin, J.F.; Liu, C.; Lawrence, K.; Bondale, N.S.; Lerner, J.; Baker, G.J.; Foulad, D.; Pechnick, R.N.; Palmer, D.; Ng, P.; Lowenstein, P.R.; Castro, M.G. Study of the Efficacy, Biodistribution, and Safety Profile of Therapeutic Gutless Adenovirus Vectors as a Prelude to a Phase I Clinical Trial for Glioblastoma. Clin. Pharmacol. Ther. 2010, 88, 204-13.
154. Kumar-Singh, R. Barriers for retinal gene therapy: separating fact from fiction. Vision Res. 2008, 48, 1671-1680.
155. Kreppel, F.; Luther, T.T.; Semkova, I.; Schraermeyer, U.; Kochanek, S. Long-term transgene expression in the RPE after gene transfer with a high-capacity adenoviral vector. Invest Ophthalmol. Vis. Sci. 2002, 43, 1965-1970.
156. Harui, A.; Roth, M.D.; Kiertscher, S.M.; Mitani, K.; Basak, S.K. Vaccination with helper-dependent adenovirus enhances the generation of transgene-specific CTL. Gene Ther. 2004, 11, 1617-1626.
157. Weaver, E.A.; Nehete, P.N.; Buchl, S.S.; Senac, J.S.; Palmer, D.; Ng, P.; Sastry, K.J.; Barry, M.A. Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines. PLoS. One 2009, 4, 5059.
158. Weaver, E.A.; Nehete, P.N.; Nehete, B.P.; Buchl, S.J.; Palmer, D.; Montefiori, D.C.; Ng, P.; Sastry, K.J.; Barry, M.A. Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines. Viruses. 2009, 1, 920-938.
159. Stern, BS.; Shoshani, W.; Pearlman, AL.; Ng, P.; Nissenson, AR.; Galun, E.; Besarab, A.; Rimler, A.; Goltzmann, H.; Miari, R.O; kun, A.; Bookay, H.; Jibly, T.; Abrameto, JA; Elhalel, M. Erythropoeisis Sustained 1 Year by the EPODURE BioPump in Patients with Chronic Kideney Disease: Further Results of PhaseI/II Proof of Concept Trial. Mol. Ther. 2010,18, S239.