This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gorziglia, M. I.
Right arrow Articles by Trapnell, B. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gorziglia, M. I.
Right arrow Articles by Trapnell, B. C.

 Previous Article  |  Next Article 

J. Virol., 06 1996, 4173-4178, Vol 70, No. 6
Copyright © 1996, American Society for Microbiology

Elimination of both E1 and E2 from adenovirus vectors further improves prospects for in vivo human gene therapy

MI Gorziglia, MJ Kadan, S Yei, J Lim, GM Lee, R Luthra and BC Trapnell
Department of Virology, Genetic Therapy, Inc., Gaithersburg, Maryland 20878, USA.

A novel recombinant adenovirus vector, Av3nBg, was constructed with deletions in adenovirus E1, E2a, and E3 regions and expressing a beta- galactosidase reporter gene. Av3nBg can be propagated at a high titer in a corresponding A549-derived cell line, AE1-2a, which contains the adenovirus E1 and E2a region genes inducibly expressed from separate glucocorticoid-responsive promoters. Av3nBg demonstrated gene transfer and expression comparable to that of Av1nBg, a first-generation adenovirus vector with deletions in E1 and E3. Several lines of evidence suggest that this vector is significantly more attenuated than E1 and E3 deletion vectors. Metabolic DNA labeling studies showed no detectable de novo vector DNA synthesis or accumulation, and metabolic protein labeling demonstrated no detectable de novo hexon protein synthesis for Av3nBg in naive A549 cells even at a multiplicity of infection of up to 3,000 PFU per cell. Additionally, naive A549 cells infected by Av3nBg did not accumulate infectious virions. In contrast, both Av1nBg and Av2Lu vectors showed DNA replication and hexon protein synthesis at multiplicities of infection of 500 PFU per cell. Av2Lu has a deletion in E1 and also carries a temperature-sensitive mutation in E2a. Thus, molecular characterization has demonstrated that the Av3nBg vector is improved with respect to the potential for vector DNA replication and hexon protein expression compared with both first- generation (Av1nBg) and second-generation (Av2Lu) adenoviral vectors. These observations may have important implications for potential use of adenovirus vectors in human gene therapy.


This article has been cited by other articles:

  • Li, Q., Guo, Y., Tan, W., Ou, Q., Wu, W.-J., Sturza, D., Dawn, B., Hunt, G., Cui, C., Bolli, R. (2007). Cardioprotection Afforded by Inducible Nitric Oxide Synthase Gene Therapy Is Mediated by Cyclooxygenase-2 via a Nuclear Factor-{kappa}B Dependent Pathway. Circulation 116: 1577-1584 [Abstract] [Full Text]  
  • Shapiro, G. S., Van Peursem, C., Ornelles, D. A., Schaack, J., DeGregori, J. (2006). Recombinant Adenoviral Vectors Can Induce Expression of p73 via the E4-orf6/7 Protein.. J. Virol. 80: 5349-5360 [Abstract] [Full Text]  
  • Narang, A. S., Mahato, R. I. (2006). Biological and biomaterial approaches for improved islet transplantation.. Pharmacol. Rev. 58: 194-243 [Abstract] [Full Text]  
  • Li, Q., Guo, Y., Tan, W., Stein, A. B., Dawn, B., Wu, W.-J., Zhu, X., Lu, X., Xu, X., Siddiqui, T., Tiwari, S., Bolli, R. (2006). Gene therapy with iNOS provides long-term protection against myocardial infarction without adverse functional consequences. Am. J. Physiol. Heart Circ. Physiol. 290: H584-H589 [Abstract] [Full Text]  
  • Ramesh, N., Ge, Y., Ennist, D. L., Zhu, M., Mina, M., Ganesh, S., Reddy, P. S., Yu, D.-C. (2006). CG0070, a Conditionally Replicating Granulocyte Macrophage Colony-Stimulating Factor-Armed Oncolytic Adenovirus for the Treatment of Bladder Cancer. Clin. Cancer Res. 12: 305-313 [Abstract] [Full Text]  
  • Zhu, M., Bristol, J. A., Xie, Y., Mina, M., Ji, H., Forry-Schaudies, S., Ennist, D. L. (2005). Linked Tumor-Selective Virus Replication and Transgene Expression from E3-Containing Oncolytic Adenoviruses. J. Virol. 79: 5455-5465 [Abstract] [Full Text]  
  • Zhang, F., Cheng, J., Hackett, N. R., Lam, G., Shido, K., Pergolizzi, R., Jin, D. K., Crystal, R. G., Rafii, S. (2004). Adenovirus E4 Gene Promotes Selective Endothelial Cell Survival and Angiogenesis via Activation of the Vascular Endothelial-Cadherin/Akt Signaling Pathway. J. Biol. Chem. 279: 11760-11766 [Abstract] [Full Text]  
  • Ehrhardt, A., Xu, H., Dillow, A. M., Bellinger, D. A., Nichols, T. C., Kay, M. A. (2003). A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 102: 2403-2411 [Abstract] [Full Text]  
  • Wu, E., Pache, L., Von Seggern, D. J., Mullen, T.-M., Mikyas, Y., Stewart, P. L., Nemerow, G. R. (2003). Flexibility of the Adenovirus Fiber Is Required for Efficient Receptor Interaction. J. Virol. 77: 7225-7235 [Abstract] [Full Text]  
  • Li, Q., Guo, Y., Xuan, Y.-T., Lowenstein, C. J., Stevenson, S. C., Prabhu, S. D., Wu, W.-J., Zhu, Y., Bolli, R. (2003). Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2-Dependent Mechanism. Circ. Res. 92: 741-748 [Abstract] [Full Text]  
  • Jakubczak, J. L., Ryan, P., Gorziglia, M., Clarke, L., Hawkins, L. K., Hay, C., Huang, Y., Kaloss, M., Marinov, A., Phipps, S., Pinkstaff, A., Shirley, P., Skripchenko, Y., Stewart, D., Forry-Schaudies, S., Hallenbeck, P. L. (2003). An Oncolytic Adenovirus Selective for Retinoblastoma Tumor Suppressor Protein Pathway-defective Tumors: Dependence on E1A, the E2F-1 Promoter, and Viral Replication for Selectivity and Efficacy. Cancer Res. 63: 1490-1499 [Abstract] [Full Text]  
  • Su, E. J., Cioffi, C. L., Stefansson, S., Mittereder, N., Garay, M., Hreniuk, D., Liau, G. (2003). Gene therapy vector-mediated expression of insulin-like growth factors protects cardiomyocytes from apoptosis and enhances neovascularization. Am. J. Physiol. Heart Circ. Physiol. 284: H1429-H1440 [Abstract] [Full Text]  
  • Wang, T., Dong, C., Stevenson, S. C., Herderick, E. E., Marshall-Neff, J., Vasudevan, S. S., Moldovan, N. I., Michler, R. E., Movva, N. R., Goldschmidt-Clermont, P. J. (2002). Overexpression of Soluble Fas Attenuates Transplant Arteriosclerosis in Rat Aortic Allografts. Circulation 106: 1536-1542 [Abstract] [Full Text]  
  • Qiao, C., Li, J., Skold, A., Zhang, X., Xiao, X. (2002). Feasibility of Generating Adeno-Associated Virus Packaging Cell Lines Containing Inducible Adenovirus Helper Genes. J. Virol. 76: 1904-1913 [Abstract] [Full Text]  
  • Zhang, W., Low, J. A., Christensen, J. B., Imperiale, M. J. (2001). Role for the Adenovirus IVa2 Protein in Packaging of Viral DNA. J. Virol. 75: 10446-10454 [Abstract] [Full Text]  
  • Jakubczak, J. L., Rollence, M. L., Stewart, D. A., Jafari, J. D., Von Seggern, D. J., Nemerow, G. R., Stevenson, S. C., Hallenbeck, P. L. (2001). Adenovirus Type 5 Viral Particles Pseudotyped with Mutagenized Fiber Proteins Show Diminished Infectivity of Coxsackie B-Adenovirus Receptor-Bearing Cells. J. Virol. 75: 2972-2981 [Abstract] [Full Text]  
  • Wang, X., Zeng, W., Murakawa, M., Freeman, M. W., Seed, B. (2000). Episomal Segregation of the Adenovirus Enhancer Sequence by Conditional Genome Rearrangement Abrogates Late Viral Gene Expression. J. Virol. 74: 11296-11303 [Abstract] [Full Text]  
  • Tripp, R. A., Jones, L., Anderson, L. J., Brown, M. P. (2000). CD40 Ligand (CD154) Enhances the Th1 and Antibody Responses to Respiratory Syncytial Virus in the BALB/c Mouse. J. Immunol. 164: 5913-5921 [Abstract] [Full Text]  
  • Von Seggern, D. J., Huang, S., Fleck, S. K., Stevenson, S. C., Nemerow, G. R. (2000). Adenovirus Vector Pseudotyping in Fiber-Expressing Cell Lines: Improved Transduction of Epstein-Barr Virus-Transformed B Cells. J. Virol. 74: 354-362 [Abstract] [Full Text]  
  • Brenner, M. (1999). Gene Transfer by Adenovectors. Blood 94: 3965-3967 [Full Text]  
  • Allen, M. D. (1999). Myocardial protection: is there a role for gene therapy?. Ann. Thorac. Surg. 68: 1924-1928 [Abstract] [Full Text]  
  • Parks, R. J., Bramson, J. L., Wan, Y., Addison, C. L., Graham, F. L. (1999). Effects of Stuffer DNA on Transgene Expression from Helper-Dependent Adenovirus Vectors. J. Virol. 73: 8027-8034 [Abstract] [Full Text]  
  • Lusky, M., Grave, L., Dieterle, A., Dreyer, D., Christ, M., Ziller, C., Furstenberger, P., Kintz, J., Ali Hadji, D., Pavirani, A., Mehtali, M. (1999). Regulation of Adenovirus-Mediated Transgene Expression by the Viral E4 Gene Products: Requirement for E4 ORF3. J. Virol. 73: 8308-8319 [Abstract] [Full Text]  
  • Tan, B. T., Wu, L., Berk, A. J. (1999). An Adenovirus-Epstein-Barr Virus Hybrid Vector That Stably Transforms Cultured Cells with High Efficiency. J. Virol. 73: 7582-7589 [Abstract] [Full Text]  
  • Harvey, B.-G., Hackett, N. R., El-Sawy, T., Rosengart, T. K., Hirschowitz, E. A., Lieberman, M. D., Lesser, M. L., Crystal, R. G. (1999). Variability of Human Systemic Humoral Immune Responses to Adenovirus Gene Transfer Vectors Administered to Different Organs. J. Virol. 73: 6729-6742 [Abstract] [Full Text]  
  • Gorziglia, M. I., Lapcevich, C., Roy, S., Kang, Q., Kadan, M., Wu, V., Pechan, P., Kaleko, M. (1999). Generation of an Adenovirus Vector Lacking E1, E2a, E3, and All of E4 except Open Reading Frame 3. J. Virol. 73: 6048-6055 [Abstract] [Full Text]  
  • Moorhead, J. W., Clayton, G. H., Smith, R. L., Schaack, J. (1999). A Replication-Incompetent Adenovirus Vector with the Preterminal Protein Gene Deleted Efficiently Transduces Mouse Ears. J. Virol. 73: 1046-1053 [Abstract] [Full Text]  
  • Roy, S., Shirley, P. S., McClelland, A., Kaleko, M. (1998). Circumvention of Immunity to the Adenovirus Major Coat Protein Hexon. J. Virol. 72: 6875-6879 [Abstract] [Full Text]  
  • Lusky, M., Christ, M., Rittner, K., Dieterle, A., Dreyer, D., Mourot, B., Schultz, H., Stoeckel, F., Pavirani, A., Mehtali, M. (1998). In Vitro and In Vivo Biology of Recombinant Adenovirus Vectors with E1, E1/E2A, or E1/E4 Deleted. J. Virol. 72: 2022-2032 [Abstract] [Full Text]  
  • Baek, S., March, K. L. (1998). Gene Therapy for Restenosis : Getting Nearer the Heart of the Matter. Circ. Res. 82: 295-305 [Abstract] [Full Text]  
  • Parks, R. J., Chen, L., Anton, M., Sankar, U., Rudnicki, M. A., Graham, F. L. (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 [Abstract] [Full Text]  
  • Ancellin, N., Colmont, C., Su, J., Li, Q., Mittereder, N., Chae, S.-S., Stefansson, S., Liau, G., Hla, T. (2002). Extracellular Export of Sphingosine Kinase-1 Enzyme. SPHINGOSINE 1-PHOSPHATE GENERATION AND THE INDUCTION OF ANGIOGENIC VASCULAR MATURATION. J. Biol. Chem. 277: 6667-6675 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»