Interferon-Inducible Mx Promoter-Driven, Long-Term Transgene Expression System of Interferon-β for Cancer Gene Therapy

Gene therapy techniques aiming to induce the long-term interferon-beta (IFN-beta) expression are desirable for inhibiting cancer growth. However, there has been no success in this regard because IFN-beta significantly inhibits transgene expression. This study used the IFN-inducible Mx promoter to promote IFN-beta expression. The pMx-IFN-beta plasmid was constructed to achieve long-term IFN-beta expression. In cultured cells transfected with the Mx promoter-driven reporter protein plasmid, IFN-beta induced concentration-dependent expression of the reporter protein. After the hydrodynamic injection of pMx-IFN-beta into mice, the serum concentration of IFN-beta was maintained at >= 100 pg/mL for >1 month. IFN-beta expression was significantly suppressed by the co-injection of small interfering RNA targeting the interferon-alpha/beta receptor (IFNAR), suggesting that IFN-beta binding to IFNAR increased IFN-beta expression. Moreover, the hydrodynamic injection of pMx-IFN-beta significantly suppressed the growth of colon26 tumors in mice. In contrast, a conventional promoter-driven plasmid was less effective than pMx-IFN-beta 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-beta and represents a potential tool for cancer gene therapy.