New insights into stability of recombinant adenovirus vector genomes in mammalian cells

European Journal of Cell Biology

Volumn 91, Issue 1, 2012, Pages 2-9

  Rauschhuber, Christina ^a   Noske, Nadja ^a   Ehrhardt, Anja ^a  

^a UNIVERSITY OF MUNICH   (Germany)

Author keywords

Adenovirus; Episomal; Gene therapy; Genome; High capacity adenoviral vector; PhiC31; Sleeping Beauty transposase; Somatic integration; Stability

Indexed keywords

ADENOVIRUS VECTOR;

CELL NUCLEUS; DNA INTEGRATION; DNA SEQUENCE; EPISOME; GENE INSERTION; MAMMAL CELL; NONHUMAN; PERSISTENT VIRUS INFECTION; PRIORITY JOURNAL; SHORT SURVEY; TRANSGENE; VIRUS GENE; VIRUS RECOMBINANT;

ADENOVIRIDAE; ANIMALS; CHROMOSOMAL INSTABILITY; CHROMOSOMES; EXTRACHROMOSOMAL INHERITANCE; GENE THERAPY; GENETIC DISEASES, INBORN; GENETIC ENGINEERING; GENETIC VECTORS; GENOME, VIRAL; HUMANS; MAMMALS; PLASMIDS; RECOMBINASES; TRANSGENES; TRANSPOSASES; VIRUS INTEGRATION;

ADENOVIRIDAE; ANIMALIA; EUKARYOTA; MAMMALIA;

EID: 84855949413     PISSN: 01719335     EISSN: 16181298     Source Type: Journal    
DOI: 10.1016/j.ejcb.2011.01.006     Document Type: Short Survey

References (96)

1. Anderson C.W., Young M.E., Flint S.J. Characterization of the adenovirus 2 virion protein, mu. Virology 1989, 172:506-512.
2. Angeletti P.C., Engler J.A. Adenovirus preterminal protein binds to the CAD enzyme at active sites of viral DNA replication on the nuclear matrix. J. Virol. 1998, 72:2896-2904.
3. Bangari D.S., Mittal S.K. Current strategies and future directions for eluding adenoviral vector immunity. Curr. Gene Ther. 2006, 6:215-226.
4. Benihoud K., Yeh P., Perricaudet M. Adenovirus vectors for gene delivery. Curr. Opin. Biotechnol. 1999, 10:440-447.
5. Berget S.M., Moore C., Sharp P.A. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. U. S. A. 1977, 74:3171-3175.
6. Boyer J., Rohleder K., Ketner G. Adenovirus E4 34k and E4 11k inhibit double strand break repair and are physically associated with the cellular DNA-dependent protein kinase. Virology 1999, 263:307-312.
7. 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.
8. 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.
9. Burg J.L., Schweitzer J., Daniell E. Introduction of superhelical turns into DNA by adenoviral core proteins and chromatin assembly factors. J. Virol. 1983, 46:749-755.
10. 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.
11. Cao H., Koehler D.R., Hu J. Adenoviral vectors for gene replacement therapy. Viral Immunol. 2004, 17:327-333.
12. Carson C.T., Schwartz R.A., Stracker T.H., Lilley C.E., Lee D.V., Weitzman M.D. The Mre11 complex is required for ATM activation and the G2/M checkpoint. EMBO J. 2003, 22:6610-6620.
13. Chalberg T.W., Portlock J.L., Olivares E.C., Thyagarajan B., Kirby P.J., Hillman R.T., Hoelters J., Calos M.P. Integration specificity of phage phiC31 integrase in the human genome. J. Mol. Biol. 2006, 357:28-48.
14. Chatterjee P.K., Vayda M.E., Flint S.J. Interactions among the three adenovirus core proteins. J. Virol. 1985, 55:379-386.
15. Daniell E., Groff D.E., Fedor M.J. Adenovirus chromatin structure at different stages of infection. Mol. Cell. Biol. 1981, 1:1094-1105.
16. Danthinne X., Imperiale M.J. Production of first generation adenovirus vectors: a review. Gene Ther. 2000, 7:1707-1714.
17. Davison A.J., Benko M., Harrach B. Genetic content and evolution of adenoviruses. J. Gen. Virol. 2003, 84:2895-2908.
18. Ehrhardt A., Engler J.A., Xu H., Cherry A.M., Kay M.A. Molecular analysis of chromosomal rearrangements in mammalian cells after phiC31-mediated integration. Hum. Gene Ther. 2006, 17:1077-1094.
19. Ehrhardt A., Kay M.A. A new adenoviral helper-dependent vector results in long-term therapeutic levels of human coagulation factor IX at low doses in vivo. Blood 2002, 99:3923-3930.
20. Ehrhardt A., Xu H., Dillow A.M., Bellinger D.A., Nichols T.C., Kay M.A. A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 2003, 102:2403-2411.
21. 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.
22. Ehrhardt A., Xu H., Huang Z., Engler J.A., Kay M.A. A direct comparison of two nonviral gene therapy vectors for somatic integration: in vivo evaluation of the bacteriophage integrase phiC31 and the Sleeping Beauty transposase. Mol. Ther. 2005, 11:695-706.
23. Ehrhardt A., Yant S.R., Giering J.C., Xu H., Engler J.A., Kay M.A. Somatic integration from an adenoviral hybrid vector into a hot spot in mouse liver results in persistent transgene expression levels in vivo. Mol. Ther. 2007, 15:146-156.
24. Fredman J.N., Engler J.A. Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro. J. Virol. 1993, 67:3384-3395.
25. Goncalves M.A., Holkers M., Cudre-Mauroux C., van Nierop G.P., Knaan-Shanzer S., van der Velde I., Valerio D., de Vries A.A. Transduction of myogenic cells by retargeted dual high-capacity hybrid viral vectors: robust dystrophin synthesis in Duchenne muscular dystrophy muscle cells. Mol. Ther. 2006, 13:976-986.
26. Goncalves M.A., Holkers M., van Nierop G.P., Wieringa R., Pau M.G., de Vries A.A. Targeted chromosomal insertion of large DNA into the human genome by a fiber-modified high-capacity adenovirus-based vector system. PLoS One 2008, 3:e3084.
27. Gorziglia M.I., Kadan M.J., Yei S., Lim J., Lee G.M., Luthra R., Trapnell B.C. Elimination of both E1 and E2 from adenovirus vectors further improves prospects for in vivo human gene therapy. J. Virol. 1996, 70:4173-4178.
28. Graham F.L., Smiley J., Russell W.C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. 1977, 36:59-74.
29. Groth A.C., Olivares E.C., Thyagarajan B., Calos M.P. A phage integrase directs efficient site-specific integration in human cells. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:5995-6000.
30. Harui A., Suzuki S., Kochanek S., Mitani K. Frequency and stability of chromosomal integration of adenovirus vectors. J. Virol. 1999, 73:6141-6146.
31. Hausl M.A., Zhang W., Muether N., Rauschhuber C., Franck H.G., Merricks E., Nichols T.C., Kay M.A., Ehrhardt A. Hyperactive Sleeping Beauty transposase enables persistent phenotypic correction in mice and a canine model for hemophilia B. Mol. Ther. 2010, 18:1896-1906.
32. Hillgenberg M., Schnieders F., Loser P., Strauss M. System for efficient helper-dependent minimal adenovirus construction and rescue. Hum. Gene Ther. 2001, 12:643-657.
33. Hochstein N., Muiznieks I., Mangel L., Brondke H., Doerfler W. Epigenetic status of an adenovirus type 12 transgenome upon long-term cultivation in hamster cells. J. Virol. 2007, 81:5349-5361.
34. Ivics Z., Hackett P.B., Plasterk R.H., Izsvak Z. Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 1997, 91:501-510.
35. Ivics Z., Katzer A., Stuwe E.E., Fiedler D., Knespel S., Izsvak Z. Targeted Sleeping Beauty transposition in human cells. Mol. Ther. 2007, 15:1137-1144.
36. 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.
37. Jager L., Hausl M.A., Rauschhuber C., Wolf N.M., Kay M.A., Ehrhardt A. A rapid protocol for construction and production of high-capacity adenoviral vectors. Nat. Protoc. 2009, 4:547-564.
38. Jayaram S., Bridge E. Genome concatenation contributes to the late gene expression defect of an adenovirus E4 mutant. Virology 2005, 342:286-296.
39. Kawano R., Ishizaki M., Maeda Y., Uchida Y., Kimura E., Uchino M. Transduction of full-length dystrophin to multiple skeletal muscles improves motor performance and life span in utrophin/dystrophin double knockout mice. Mol. Ther. 2008, 16:825-831.
40. 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.
41. Kochanek S., Schiedner G., Volpers C. High-capacity 'gutless' adenoviral vectors. Curr. Opin. Mol. Ther. 2001, 3:454-463.
42. Kreppel F., Kochanek S. Long-term transgene expression in proliferating cells mediated by episomally maintained high-capacity adenovirus vectors. J. Virol. 2004, 78:9-22.
43. Kuhstoss S., Rao R.N. Analysis of the integration function of the streptomycete bacteriophage phi C31. J. Mol. Biol. 1991, 222:897-908.
44. Lewinski M.K., Yamashita M., Emerman M., Ciuffi A., Marshall H., Crawford G., Collins F., Shinn P., Leipzig J., Hannenhalli S., Berry C.C., Ecker J.R., Bushman F.D. Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog. 2006, 2:e60.
45. Liu J., Jeppesen I., Nielsen K., Jensen T.G. PhiC31 integrase induces chromosomal aberrations in primary human fibroblasts. Gene Ther. 2006, 13:1188-1190.
46. Lombardo A., Genovese P., Beausejour C.M., Colleoni S., Lee Y.L., Kim K.A., Ando D., Urnov F.D., Galli C., Gregory P.D., Holmes M.C., Naldini L. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat. Biotechnol. 2007, 25:1298-1306.
47. 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.
48. Maione D., Della Rocca C., Giannetti P., D'Arrigo R., Liberatoscioli L., Franlin L.L., Sandig V., Ciliberto G., La Monica 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.
49. Mates L., Chuah M.K., Belay E., Jerchow B., Manoj N., Acosta-Sanchez A., Grzela D.P., Schmitt A., Becker K., Matrai J., Ma L., Samara-Kuko E., Gysemans C., Pryputniewicz D., Miskey C., Fletcher B., VandenDriessche T., Ivics Z., Izsvak Z. Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates. Nat. Genet. 2009, 41:753-761.
50. Medina-Kauwe L.K. Endocytosis of adenovirus and adenovirus capsid proteins. Adv. Drug Deliv. Rev. 2003, 55:1485-1496.
51. Middleton T., Sugden B. Retention of plasmid DNA in mammalian cells is enhanced by binding of the Epstein-Barr virus replication protein EBNA1. J. Virol. 1994, 68:4067-4071.
52. Miller D.G., Petek L.M., Russell D.W. Adeno-associated virus vectors integrate at chromosome breakage sites. Nat. Genet. 2004, 36:767-773.
53. Morral N., O'Neal W., Rice K., Leland M., Kaplan J., Piedra P.A., Zhou H., Parks R.J., Velji R., Aguilar-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.
54. Morral N., Parks R.J., Zhou H., Langston C., Schiedner G., Quinones J., Graham F.L., Kochanek S., Beaudet A.L. High doses of a helper-dependent adenoviral vector yield supraphysiological levels of alpha1-antitrypsin with negligible toxicity. Hum. Gene Ther. 1998, 9:2709-2716.
55. Morsy M.A., Gu M., Motzel S., Zhao J., Lin J., Su Q., Allen H., Franlin L., Parks R.J., Graham F.L., Kochanek S., Bett A.J., Caskey C.T. An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:7866-7871.
56. Muether N., Noske N., Ehrhardt A. Viral hybrid vectors for somatic integration - are they the better solution?. Viruses 2009, 1:1295-1324.
57. Murphy S.J., Chong H., Bell S., Diaz R.M., Vile R.G. Novel integrating adenoviral/retroviral hybrid vector for gene therapy. Hum. Gene Ther. 2002, 13:745-760.
58. Nakai H., Montini E., Fuess S., Storm T.A., Grompe M., Kay M.A. AAV serotype 2 vectors preferentially integrate into active genes in mice. Nat. Genet. 2003, 34:297-302.
59. Nelson J.E., Kay M.A. Persistence of recombinant adenovirus in vivo is not dependent on vector DNA replication. J. Virol. 1997, 71:8902-8907.
60. Ohbayashi F., Balamotis M.A., Kishimoto A., Aizawa E., Diaz A., Hasty P., Graham F.L., Caskey C.T., Mitani K. Correction of chromosomal mutation and random integration in embryonic stem cells with helper-dependent adenoviral vectors. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:13628-13633.
61. Olivares E.C., Hollis R.P., Chalberg T.W., Meuse L., Kay M.A., Calos M.P. Site-specific genomic integration produces therapeutic factor IX levels in mice. Nat. Biotechnol. 2002, 20:1124-1128.
62. Palmer D., Ng P. Improved system for helper-dependent adenoviral vector production. Mol. Ther. 2003, 8:846-852.
63. 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.
64. 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.
65. 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.
66. Recchia A., Parks R.J., Lamartina S., Toniatti C., Pieroni L., Palombo F., Ciliberto G., Graham F.L., Cortese R., La Monica N., Colloca S. Site-specific integration mediated by a hybrid adenovirus/adeno-associated virus vector. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:2615-2620.
67. Ross P.J., Kennedy M.A., Parks R.J. Host cell detection of noncoding stuffer DNA contained in helper-dependent adenovirus vectors leads to epigenetic repression of transgene expression. J. Virol. 2009, 83:8409-8417.
68. Ruben M., Bacchetti S., Graham F. Covalently closed circles of adenovirus 5 DNA. Nature 1983, 301:172-174.
69. Russell W.C. Update on adenovirus and its vectors. J. Gen. Virol. 2000, 81:2573-2604.
70. Schiedner G., Morral N., Parks R.J., Wu Y., Koopmans S.C., Langston C., Graham F.L., Beaudet A.L., Kochanek S. Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity. Nat. Genet. 1998, 18:180-183.
71. Schroder A.R., Shinn P., Chen H., Berry C., Ecker J.R., Bushman F. HIV-1 integration in the human genome favors active genes and local hotspots. Cell 2002, 110:521-529.
72. Schwarzwaelder K., Howe S.J., Schmidt M., Brugman M.H., Deichmann A., Glimm H., Schmidt S., Prinz C., Wissler M., King D.J., Zhang F., Parsley K.L., Gilmour K.C., Sinclair J., Bayford J., Peraj R., Pike-Overzet K., Staal F.J., de Ridder D., Kinnon C., Abel U., Wagemaker G., Gaspar H.B., Thrasher A.J., von Kalle C. Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo. J. Clin. Invest. 2007, 117:2241-2249.
73. Sergeant A., Tigges M.A., Raskas H.J. Nucleosome-like structural subunits of intranuclear parental adenovirus type 2 DNA. J. Virol. 1979, 29:888-898.
74. Soifer H.S., Kasahara N. Retrotransposon-adenovirus hybrid vectors: efficient delivery and stable integration of transgenes via a two-stage mechanism. Curr. Gene Ther. 2004, 4:373-384.
75. Stephen S.L., Montini E., Sivanandam V.G., Al-Dhalimy M., Kestler H.A., Finegold M., Grompe M., Kochanek S. Chromosomal integration of adenoviral vector DNA in vivo. J. Virol. 2010, 84:9987-9994.
76. Stephen S.L., Sivanandam V.G., Kochanek S. Homologous and heterologous recombination between adenovirus vector DNA and chromosomal DNA. J. Gene Med. 2008, 10:1176-1189.
77. Stracker T.H., Carson C.T., Weitzman M.D. Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature 2002, 418:348-352.
78. Stracker T.H., Lee D.V., Carson C.T., Araujo F.D., Ornelles D.A., Weitzman M.D. Serotype-specific reorganization of the Mre11 complex by adenoviral E4orf3 proteins. J. Virol. 2005, 79:6664-6673.
79. Suomalainen M., Nakano M.Y., Keller S., Boucke K., Stidwill R.P., Greber U.F. Microtubule-dependent plus- and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J. Cell Biol. 1999, 144:657-672.
80. Suzuki K., Mitsui K., Aizawa E., Hasegawa K., Kawase E., Yamagishi T., Shimizu Y., Suemori H., Nakatsuji N., Mitani K. Highly efficient transient gene expression and gene targeting in primate embryonic stem cells with helper-dependent adenoviral vectors. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:13781-13786.
81. Tate V.E., Philipson L. Parental adenovirus DNA accumulates in nucleosome-like structures in infected cells. Nucleic Acids Res. 1979, 6:2769-2785.
82. 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.
83. Thyagarajan B., Olivares E.C., Hollis R.P., Ginsburg D.S., Calos M.P. Site-specific genomic integration in mammalian cells mediated by phage phiC31 integrase. Mol. Cell. Biol. 2001, 21:3926-3934.
84. 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.
85. Tollefson A.E., Scaria A., Hermiston T.W., Ryerse J.S., Wold L.J., Wold W.S. The adenovirus death protein (E3-11.6K) is required at very late stages of infection for efficient cell lysis and release of adenovirus from infected cells. J. Virol. 1996, 70:2296-2306.
86. Vigdal T.J., Kaufman C.D., Izsvak Z., Voytas D.F., Ivics Z. Common physical properties of DNA affecting target site selection of Sleeping Beauty and other Tc1/mariner transposable elements. J. Mol. Biol. 2002, 323:441-452.
87. 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 Rooijen 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.
88. Wang H., Liu Y., Li Z., Tuve S., Stone D., Kalyushniy O., Shayakhmetov D., Verlinde C.L., Stehle T., McVey J., Baker A., Peng K.W., Roffler S., Lieber A. In vitro and in vivo properties of adenovirus vectors with increased affinity to CD46. J. Virol. 2008, 82:10567-10579.
89. Weiden M.D., Ginsberg H.S. Deletion of the E4 region of the genome produces adenovirus DNA concatemers. Proc. Natl. Acad. Sci. U. S. A. 1994, 91:153-157.
90. Weitzman M.D. Functions of the adenovirus E4 proteins and their impact on viral vectors. Front. Biosci. 2005, 10:1106-1117.
91. Yant S.R., Meuse L., Chiu W., Ivics Z., Izsvak Z., Kay M.A. Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system. Nat. Genet. 2000, 25:35-41.
92. Yant S.R., Ehrhardt A., Mikkelsen J.G., Meuse L., Pham T., Kay M.A. Transposition from a gutless adeno-transposon vector stabilizes transgene expression in vivo. Nat. Biotechnol. 2002, 20:999-1005.
93. Yant S.R., Wu X., Huang Y., Garrison B., Burgess S.M., Kay M.A. High-resolution genome-wide mapping of transposon integration in mammals. Mol. Cell. Biol. 2005, 25:2085-2094.
94. Yant S.R., Huang Y., Akache B., Kay M.A. Site-directed transposon integration in human cells. Nucleic Acids Res. 2007, 35:e50.
95. Zhang Y., Bergelson J.M. Adenovirus receptors. J. Virol. 2005, 79:12125-12131.
96. Zheng C., Baum B.J., Iadarola M.J., O'Connell B.C. Genomic integration and gene expression by a modified adenoviral vector. Nat. Biotechnol. 2000, 18:176-180.