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Journal of Virology, July 2002, p. 7343-7348, Vol. 76, No. 14
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.14.7343-7348.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Le Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel Dieu de Québec, Centre Hospitalier Universitaire de Québec, Québec G1R 2J6, Canada
Received 1 February 2002/ Accepted 2 April 2002
The development of suicide gene therapy with gene products that are directly toxic to cells, such as the A subunit of diphtheria toxin (DT-A), has been hampered by the difficulty of engineering recombinant viruses. DT-A is a strong inhibitor of protein synthesis that acts by ADP-ribosylating elongation factor 2, and a low level of DT-A expression in virus producer cells prevents the production of recombinant virus. We analyzed here the natural resistance of packaging cells to DT-A toxicity, and we report that PG13 and PA317 packaging cell lines are resistant to H21G, a DT-A mutant. PG13 cells produce recombinant H21G virus that efficiently kills a variety of human tumor cells. Our finding indicates that PG13 packaging cells provide a new potential for the development of DT-A-based suicide gene therapy.
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