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GENE THERAPY

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Steven F. Farina, Guang-ping Gao, Z. Q. Xiang, John J. Rux, Roger M. Burnett, Mauricio R. Alvira, Jonathan Marsh, Hildegund C. J. Ertl, James M. Wilson
Steven F. Farina
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania, and
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Guang-ping Gao
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania, and
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Z. Q. Xiang
The Wistar Institute, Philadelphia, Pennsylvania
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John J. Rux
The Wistar Institute, Philadelphia, Pennsylvania
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Roger M. Burnett
The Wistar Institute, Philadelphia, Pennsylvania
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Mauricio R. Alvira
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania, and
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Jonathan Marsh
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania, and
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Hildegund C. J. Ertl
The Wistar Institute, Philadelphia, Pennsylvania
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James M. Wilson
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania, and
The Wistar Institute, Philadelphia, Pennsylvania
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DOI: 10.1128/JVI.75.23.11603-11613.2001
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ABSTRACT

An adenovirus previously isolated from a mesenteric lymph node from a chimpanzee was fully sequenced and found to be similar in overall structure to human adenoviruses. The genome of this virus, called C68, is 36,521 bp in length and is most similar to subgroup E of human adenovirus, with 90% identity in most adenovirus type 4 open reading frames that have been sequenced. Substantial differences in the hexon hypervariable regions were noted between C68 and other known adenoviruses, including adenovirus type 4. Neutralizing antibodies to C68 were highly prevalent in sera from a population of chimpanzees, while sera from humans and rhesus monkeys failed to neutralize C68. Furthermore, infection with C68 was not neutralized from sera of mice immunized with human adenovirus serotypes 2, 4, 5, 7, and 12. A replication-defective version of C68 was created by replacing the E1a and E1b genes with a minigene cassette; this vector was efficiently transcomplemented by the E1 region of human adenovirus type 5. C68 vector transduced a number of human and murine cell lines. This nonhuman adenoviral vector is sufficiently similar to human serotypes to allow growth in 293 cells and transduction of cells expressing the coxsackievirus and adenovirus receptor. As it is dissimilar in regions such as the hexon hypervariable domains, C68 vector avoids significant cross-neutralization by sera directed against human serotypes.

  • Copyright © 2001 American Society for Microbiology
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Replication-Defective Vector Based on a Chimpanzee Adenovirus
Steven F. Farina, Guang-ping Gao, Z. Q. Xiang, John J. Rux, Roger M. Burnett, Mauricio R. Alvira, Jonathan Marsh, Hildegund C. J. Ertl, James M. Wilson
Journal of Virology Dec 2001, 75 (23) 11603-11613; DOI: 10.1128/JVI.75.23.11603-11613.2001

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Replication-Defective Vector Based on a Chimpanzee Adenovirus
Steven F. Farina, Guang-ping Gao, Z. Q. Xiang, John J. Rux, Roger M. Burnett, Mauricio R. Alvira, Jonathan Marsh, Hildegund C. J. Ertl, James M. Wilson
Journal of Virology Dec 2001, 75 (23) 11603-11613; DOI: 10.1128/JVI.75.23.11603-11613.2001
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KEYWORDS

Adenoviridae
Capsid Proteins
Genetic Vectors

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