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Journal of Virology, January 2000, p. 505-512, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Canine Adenovirus Vectors: an Alternative for Adenovirus-Mediated Gene Transfer

Eric J. Kremer,* Sylvie Boutin, Miguel Chillon, and Olivier Danos

Programme Thérapie Génique, Généthon III and CNRS URA 1923, 91002 Evry, France

Received 18 June 1999/Accepted 24 September 1999

Preclinical studies have shown that gene transfer following readministration of viral vectors is often inefficient due to the presence of neutralizing antibodies. Vectors derived from ubiquitous human adenoviruses may have limited clinical use because preexisting humoral and cellular immunity is found in 90% of the population. Furthermore, risks associated with the use of human adenovirus vectors, such as the need to immunosuppress or tolerize patients to a potentially debilitating virus, are avoidable if efficient nonhuman adenovirus vectors are feasible. Plasmids containing recombinant canine adenovirus (CAV) vectors from which the E1 region had been deleted were generated and transfected into a CAV E1-transcomplementing cell line. Vector stocks, with titers greater than or equal to those obtained with human adenovirus vectors, were free of detectable levels of replication-competent CAV and had a low particle-to-transduction unit ratio. CAV vectors were replication defective in all cell lines tested, transduced human-derived cells at an efficiency similar to that of a comparable human adenovirus type 5 vector, and are amenable to in vivo use. Importantly, 49 of 50 serum samples from healthy individuals did not contain detectable levels of neutralizing CAV antibodies.

* Corresponding author. Mailing address: Généthon III/CNRS URA 1923, 1 bis, rue de l'Internationale, 91002 Evry, France. Phone: 33 (0) 1 69 47 10 30. Fax: 33 (0) 1 60 77 86 98. E-mail: ekremer{at}genethon.fr.

Journal of Virology, January 2000, p. 505-512, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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