PG13 packaging cells produce recombinant retroviruses carrying a diphtheria toxin mutant which kills cancer cells.
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.
Qiao
Jian
J
Le Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel Dieu de Québec, Centre Hospitalier Universitaire de Québec, Québec G1R 2J6, Canada.
Caruso
Manuel
M
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004167:Diphtheria Toxin / Q000235:genetics / Q000633:toxicity*; D015316:Genetic Therapy / Q000379:methods*; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000633:toxicity*; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000502:physiology / Q000821:virology; D019065:Virus Assembly
D004167:Diphtheria Toxin; D010446:Peptide Fragments; C029795:diphtheria toxin fragment A