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

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

Human gene therapy (2016-08-09)
Atsushi Hamana, Yuki Takahashi, Makiya Nishikawa, Yoshinobu Takakura
초록

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.

MATERIALS
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Sigma-Aldrich
MISSION® esiRNA, targeting human IFNAR1