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Highly efficient eradication of intracranial glioblastoma using Eg5 siRNA combined with HVJ envelope

Gene Therapy volume 16, pages 1465–1476 (2009)Cite this article

Abstract

Hemagglutinating virus of Japan envelope (HVJ-E) vector with inactivated replication-defective Sendai virus was originally developed as a versatile drug delivery system. Recently, we have shown the direct tumor-killing activity of HVJ-E itself without therapeutic molecules in prostate cancer cells. Although human glioblastoma cells were also sensitive to HVJ-E treatment, complete eradication was not achieved using HVJ-E alone. Here, to develop more effective therapeutic strategy of glioblastoma, we enhanced the anti-tumor activity by incorporating Short interfering RNA (siRNA) of mitotic motor protein Eg5 into HVJ-E. Treatment with HVJ-E-containing Eg5 siRNA induced monopolar spindle formation and resulted in cell-cycle arrest and apoptosis. When HVJ-E-containing Eg5 siRNA was directly injected into an intradermal tumor xenograft, all mice became tumor-free. Similar results were observed in the intracranial tumor xenografts. The survival time of treated mice was significantly prolonged when HVJ-E was used. Histological examination showed that tumors remained in the brain after treatment with HVJ-E-containing negative control siRNA, but no tumors were detected after treatment with HVJ-E-containing Eg5 siRNA. This remarkable anti-tumor response was likely due to a synergistic effect of Eg5 siRNA and HVJ-E. Thus, this combination shows promise as an attractive novel therapy for glioblastoma.

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Acknowledgements

This work was supported by the Northern Osaka (Saito) Biomedical Knowledge-Based Cluster Creation Project, and Special Coordination Funds for Promoting Science by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan

    M Matsuda & Y Kaneda

  2. Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    M Matsuda, T Yamamoto & A Matsumura

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  1. M Matsuda
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Correspondence to Y Kaneda.

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Matsuda, M., Yamamoto, T., Matsumura, A. et al. Highly efficient eradication of intracranial glioblastoma using Eg5 siRNA combined with HVJ envelope. Gene Ther 16, 1465–1476 (2009). https://doi.org/10.1038/gt.2009.99

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