Prolonged circulation half-life of interferon γ activity by gene delivery of interferon γ–serum albumin fusion protein in mice
✍ Scribed by Noriko Miyakawa; Makiya Nishikawa; Yuki Takahashi; Mitsuru Ando; Masayuki Misaka; Yoshihiko Watanabe; Yoshinobu Takakura
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 234 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
Gene delivery of mouse interferon (IFN) ( has been shown to inhibit metastatic tumor growth and onset of atopic dermatitis in mouse models. In this study, we tried to increase the circulation half-life of IFN( after its gene delivery by designing a novel fusion protein of IFN( with mouse serum albumin (MSA). Western blot analysis confirmed that IFN(-MSA was expressed as a fusion protein, but hardly formed dimer as IFN( did. The biological activity of IFN(-MSA, which was examined using a plasmid expressing luciferase under the control of gamma-activated sequence elements, was about 200-fold lower than the activity of IFN(. Intravenous injection of the proteins into mice confirmed that the circulation half-life of IFN( was significantly prolonged by the modification. A hydrodynamic injection of a plasmid expressing IFN(-MSA resulted in a sustained concentration in mouse serum; it resulted in about sixfold greater area under the concentration-time curve and about threefold longer mean residence time of IFN( activity than those of IFN(. Gene delivery of IFN(-MSA inhibited tumor metastasis to a similar level to that of IFN( despite the reduced activity of IFN(-MSA. These results indicate that gene delivery of IFN(-MSA is a promising approach to prolong the circulation half-life of IFN( activity.