Adenovirus vectors deleted for genes essential for viral DNA replication
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Adenovirus (Ad) gene therapy vectors made replication defective by deletion of the E1 region (first-generation vectors) induce high-level inflammation that leads to loss of both transduced gene expression and transduced cells. First-generation vectors were initially considered to be incapable of viral DNA replication, but it is necessary to delete one or more of the genes, all in the E2 transcription unit, that encode proteins essential for Ad DNA replication to completely eliminate viral DNA replication. Vectors deleted for one or more of the E2 genes (second-generation vectors) induce reduced levels of inflammation in certain animal models and offer promise for understanding the mechanisms by which adenovirus vectors induce inflammation and how inflammation can be inhibited. While first-generation vectors dominated the initial human gene therapy trials using adenovirus vectors, second-generation vectors may offer greater promise and greater safety for clinical studies.
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Vectors with both E1 and E4 units deleted result in lower immune responses.
“Vectors with both E1 and E4 units deleted result in lower immune responses.”
From Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges (2020) · cites this paper as [69]
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Potential of helper-dependent adenoviral vectors in modulating airway innate immunity.
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Gene therapy in cutaneous wound healing
Hirsch, T. (2006) · Frontiers in bioscience · doi:10.2741/2251 · Cited by 15 · see citing works
Gene therapy approaches for equine osteoarthritis
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E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor
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- Authors
- Schaack, J.
- Affiliations
- University of Colorado Denver (US)
- Corresponding author
- Schaack, Jerome,
- Venue
- Frontiers in Bioscience
- Publisher
- IMR Press
- Published
- 2005
- Volume
- 10
- Issue
- 1-3
- Pages
- 1146
- ISSN
- 1093-4715 (ISSN-L)
- 1093-9946
- DOI
- 10.2741/1607
- OpenAlex
- W20894145
- Cited by
- 26
- References
- 95
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 3 · 2017: 1 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 0.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Frontiers in bioscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- adenoviral vector, gene therapy vectors, viral DNA replication, replication-defective vectors, inflammation, vector safety
- MeSH terms
- Adenoviridae, Animals, DNA Replication, DNA, Viral, Genetic Vectors, Humans, Virus Replication, Genetic Therapy, Gene Deletion, Adenovirus E2 Proteins
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