Abstract
Hydrodynamic injection of pmCMV(enh) -hEF-1(prom) -muIFN-γ, a plasmid DNA (pDNA) expressing murine interferon (IFN)-γ with a murine cytomegalovirus (mCMV) enhancer and a human elongation factor (EF)-1 promoter, has been proven effective for the treatment of cancer and atopic dermatitis in mice. However, the initial peak of IFN-γ soon after injection was quite high compared to the steady level for subsequent periods, which could cause unwanted adverse effects. Therefore, in the present study, aiming to optimize the efficacy/side-effect ratio of IFN-γ gene transfer, we have developed plasmid vectors encoding murine IFN-γ under the control of different combinations of promoter and enhancer sequences. The promoter and enhancer sequence of pmCMV(enh) -hEF-1(prom) -huIFN-γ, a prototype plasmid expressing human IFN-γ, was replaced or deleted to obtain various pDNAs. To assess the transgene expression profile, each pDNA was delivered to mice by hydrodynamic injection and the serum IFN-γ concentration was measured periodically. On the basis of the results obtained, murine IFN-γ expressing pDNAs were constructed and the body weight change was monitored as an indicator of adverse effects. The prototype pmCMV(enh) -hEF-1(prom) -huIFN-γ sho...Continue Reading
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