DNA damaging agents improve stable gene transfer efficiency in mammalian cells

Gene therapy is an evolving discipline which today relies primarily on viral systems for gene transfer. The primary reason that plasmid vectors have not been widely used for gene therapy trials is their relatively low rate of stable gene transfer. We show here that both ionizing irradiation and hydrogen peroxide can each increase the gene transfer efficiency of plasmids. Hydrogen peroxide improves gene transfer in a linear dose-dependent manner. At equitoxic doses, hydrogen peroxide improves gene transfer by 20-fold over untreated cells and approximately 5 times above that seen for radiation, and this improvement correlates with both the total amount of DNA damage induced and the amount of residual damage after 4 hr of repair. These data suggest that DNA damaging agents may be useful to improve human gene therapy.