PG13 Packaging Cells Produce Recombinant Retroviruses Carrying a Diphtheria Toxin Mutant Which Kills Cancer Cells

AUTOR(ES)

Qiao, Jian

FONTE

American Society for Microbiology

RESUMO

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.

Documentos Relacionados

• A recombinant diphtheria toxin related human CD4 fusion protein specifically kills HIV infected cells which express gp120 but selects fusion toxin resistant cells which carry HIV.
• Diphtheria toxin mutant selectively kills cerebellar Purkinje neurons.
• A dominant negative mutant of PG13 suppresses transcription from a cauliflower mosaic virus 35S truncated promoter in transgenic tobacco plants.
• High-titer packaging cells producing recombinant retroviruses resistant to human serum.
• Induction of Neutralizing Antibodies against Diphtheria Toxin by Priming with Recombinant Mycobacterium bovis BCG Expressing CRM197, a Mutant Diphtheria Toxin