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Journal of Virology, February 1999, p. 1399-1410, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Mutational Analysis of the Avian Adenovirus CELO,
Which Provides a Basis for Gene Delivery Vectors
Anne-Isabelle
Michou,
Heike
Lehrmann,
Mediyha
Saltik, and
Matt
Cotten*
Institute for Molecular Pathology, 1030 Vienna, Austria
Received 23 July 1998/Accepted 20 October 1998
The avian adenovirus CELO is being developed as a gene transfer
tool. Using homologous recombination in Escherichia coli, the CELO genome was screened for regions that could be deleted and
would tolerate the insertion of a marker gene (luciferase or
enhanced green fluorescent protein). For each mutant genome, the
production of viable virus able to deliver the transgene to target
cells was monitored. A series of mutants in the genome identified a set of open reading frames that could be deleted but which
must be supplied in trans for virus replication. A region of the genome which is dispensable for viral replication and allows the
insertion of an expression cassette was identified and a vector based
on this mutation was evaluated as a gene delivery reagent. Transduction
of avian cells occurs at 10- to 100-fold greater efficiency (per virus
particle) than with an adenovirus type 5 (Ad5)-based vector
carrying the same expression cassette. Most important for gene
transfer applications, the CELO vector transduced mammalian
cells as efficiently as an Ad5 vector. The CELO vector is
exceptionally stable, can be grown inexpensively in chicken embryos, and provides a useful alternative to Ad5-based vectors.
*
Corresponding author. Mailing address: Institute for
Molecular Pathology, Dr. Bohr Gasse 7, 1030 Vienna, Austria. Phone: 43 1 797 30 526. Fax: 43 1 798 71 53. E-mail:
Cotten{at}nt.imp.univie.ac.at.
Journal of Virology, February 1999, p. 1399-1410, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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