Cited by 26Virus-based gene therapy researchRNA Interference and Gene DeliveryImmunotherapy and Immune Responses

Adenovirus vectors deleted for genes essential for viral DNA replication

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Schaack, Jerome,·2005·Frontiers in Bioscience

Abstract

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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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
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
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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