The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver.
Abstract
First-generation recombinant adenoviruses that lack E1 sequences have shown tremendous promise in animal and human models of gene therapy. Important limitations of these vectors are that recombinant gene expression is transient and inflammation occurs at the site of gene transfer. Our hypothesis for generating vectors with increased persistence is that present recombinant adenoviruses express viral proteins that stimulate cellular immune responses leading to destruction of the infected cells and repopulation of the organ with non-transgene-containing cells. This model predicts that further crippling of the virus will improve persistence and diminish pathology. We describe in this report second-generation recombinant adenoviruses harboring a beta-galactosidase-expressing transgene in which a temperature-sensitive mutation has been introduced into the E2A gene of an E1-deleted recombinant. At nonpermissive temperature, this virus fails to express late gene products, even when E1 is expressed in trans. The biology of this recombinant was studied in vivo in the context of mouse liver, a setting that is permissive for adenovirus type 5 replication. Animals that received the second-generation virus expressed the transgene for at least 70 days, whereas expression of the first-generation virus was no longer than 14 days. In addition, the inflammatory response, as measured by infiltration of CD8+ T cells, was blunted and delayed in livers infected with second-generation virus. These studies illustrate that modifications that disrupt structural protein expression in recombinant adenoviruses may be useful in enhancing their utility for gene therapy.
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“Thus, second generation vectors have been developed to attenuate chronic immune responses through the deletion of viral gene E2 and E4. The packaging capacities of these vectors are around 8 kb [31,32].”
From Viral Delivery Systems for CRISPR (2019) · cites this paper as [32]
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Cites
Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy.
Yang, Y., Nunes, F. A., Berencsi, K., Furth, E. E., Gönczöl, E., & Wilson, J. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4407 · Cited by 1,575
Self-citationA model system for in vivo gene transfer into the central nervous system using an adenoviral vector
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Gene therapy: adenovirus vectors
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Self-citationA mouse model for investigating the molecular pathogenesis of adenovirus pneumonia.
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Self-citationSelection and Preliminary Characterization of Temperature-Sensitive Mutants of Type 5 Adenovirus
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Research works printed but not linked: 6
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Cited by
Gene therapy - promises, problems and prospects
Verma, I. M., & Somia, N. (1997) · Nature · doi:10.1038/38410 · Cited by 1,681
Viral vector platforms within the gene therapy landscape
Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L., & Gao, G. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00487-6 · Cited by 1,404
Parks, R. J., Chen, L., Anton, M., Sankar, U., Rudnicki, M. A., & Graham, F. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13565 · Cited by 725
Development of Approaches to Improve Cell Survival in Myoblast Transfer Therapy
Qu, Z., Balkir, L., van Deutekom, J. C. T., Robbins, P. D., Pruchnic, R., & Huard, J. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.5.1257 · Cited by 462
The role of TGFβ1 in initiating hepatic stellate cell activation in vivo
Hellerbrand, C., Stefanovic, B., Giordano, F., Burchardt, E. R., & Brenner, D. A. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80010-5 · Cited by 393
Metadata
- Authors
- Engelhardt, J. F., Ye, X., Doranz, B., & Wilson, J. M.
- Affiliations
- Institute for Human Gene Therapy, University of Pennsylvania Medical Center, Philadelphia 19104-4268.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-06-21
- Volume
- 91
- Issue
- 13
- Pages
- 6196-6200
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 470
- References
- 11
- Language
- en
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- Engelhardt, J. F., Ye, X., Doranz, B., & Wilson, J. M. (1994). Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.13.6196
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