title: Interferon-Inducible Mx Promoter-Driven, Long-Term Transgene Expression System of Interferon-β for Cancer Gene Therapy.
abstract: Gene therapy techniques aiming to induce the long-term interferon-β (IFN-β) expression are desirable for inhibiting cancer growth. However, there has been no success in this regard because IFN-β significantly inhibits transgene expression. This study used the IFN-inducible Mx promoter to promote IFN-β expression. The pMx-IFN-β plasmid was constructed to achieve long-term IFN-β expression. In cultured cells transfected with the Mx promoter-driven reporter protein plasmid, IFN-β induced concentration-dependent expression of the reporter protein. After the hydrodynamic injection of pMx-IFN-β into mice, the serum concentration of IFN-β was maintained at ≥100 pg/mL for >1 month. IFN-β expression was significantly suppressed by the co-injection of small interfering RNA targeting the interferon-α/β receptor (IFNAR), suggesting that IFN-β binding to IFNAR increased IFN-β expression. Moreover, the hydrodynamic injection of pMx-IFN-β significantly suppressed the growth of colon26 tumors in mice. In contrast, a conventional promoter-driven plasmid was less effective than pMx-IFN-β in all the experiments. Taken together, these results indicate that the interferon-inducible Mx promoter-driven expression system effectively achieves long-term expression of IFN-β and represents a potential tool for cancer gene therapy.
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto, Japan .
authors: Atsushi
authors: A
authors: Hamana
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto, Japan .
authors: Yuki
authors: Y
authors: Takahashi
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto, Japan .
authors: Makiya
authors: M
authors: Nishikawa
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto, Japan .
authors: Yoshinobu
authors: Y
authors: Takakura
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D007371:Interferon-gamma / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D064547:Myxovirus Resistance Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic; D019076:Transgenes / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D064547:Myxovirus Resistance Proteins; D016899:Interferon-beta; D007371:Interferon-gamma
keywords: cancer gene therapy; hydrodynamic injection; interferon-b; plasmid DNA; transgene expression profile