Control of Spatiotemporal Distribution of Interferon γ by Genetically Fusing Functional Peptides

Mitsuru Ando, Yuki Takahashi, Makiya Nishikawa, Yoshinobu Takakura
2012 Yakugaku zasshi  
Type II interferon (IFNg) is a representative Th1 cytokine and it possesses a variety of functions, including immune regulation, antiviral and antitumor activity. Because of its multifunctional nature, IFNg is expected to be applied to the treatment of autoimmune diseases, cancer and viral infection. Although IFNg has therapeutic potential for such diseases, the clinical use of IFNg has been limited due to its short in vivo half-life and serious adverse eŠects. In contrast, gene delivery of
more » ... ene delivery of IFNg is an alternative approach to increasing the retention time of IFNg. To extend transgene expression after plasmid DNA (pDNA) gene transfer, we designed and developed pDNA with varying numbers of CpG motifs. CpG-reduced pDNA resulted in more durable transgene expression than its CpG replete counterpart in mice. Comparison of the eŠect of promoter/enhancer elements on transgene expression showed that ROSA26 promoter-mediated IFNg expression was safe because of the lack of an initial surge after hydrodynamic gene transfer. We also designed an IFNg-mouse serum albumin (MSA) fusion protein, IFNg-MSA. Gene transfer of this fusion protein resulted in a sustained concentration of IFNg fusion protein in mouse serum, and inhibited tumor metastasis in mice. These results provide experimental evidence that IFNg gene therapy can be a useful treatment for a variety of diseases.
doi:10.1248/yakushi.12-00235-4 pmid:23208047 fatcat:gfvosfu73ffg3at53bluuw7rlm