Hidetoshi Mima

Osaka University, Ōsaka-shi, Osaka-fu, Japan

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Publications (3)14.8 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The hemagglutinating virus of Japan envelope (HVJ-E; Sendai virus) vector derived from inactivated HVJ particles can be used to deliver DNA, proteins, and drugs into cells both in vitro and in vivo. HVJ-E is capable of delivering bleomycin, an anticancer drug, to various cancer cell lines, thereby producing 300-fold greater cytotoxicity than administration of bleomycin alone. In a mouse model of peritoneally disseminated colon cancer, we injected HVJ-E containing the luciferase gene into the peritoneum. Unexpectedly, luciferase gene expression was not observed within the tumor deposits or any organs. However, when combined with cationized gelatin (CG), CG-HVJ-E produced a high level of luciferase gene expression primarily within the tumor deposits. Forty-eight hours after introducing colon cancer cells into the peritoneum of experimental mice, CG-HVJ-E with or without bleomycin was injected into the abdominal cavity. Following six injections of bleomycin-incorporated CG-HVJ-E, complete responses were observed in 40% of the mice examined. All of the mice that received either empty CG-HVJ-E or bleomycin alone died within 40 days of having cancer cells introduced into the peritoneum. When the mice with complete responses were rechallenged with colon cancer cells from the same cell line, no tumors developed. Thus, CG-HVJ-E may suppress peritoneal dissemination of cancer.
    Molecular Cancer Therapeutics 05/2006; 5(4):1021-8. · 5.60 Impact Factor
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    ABSTRACT: Vector development is critical for the advancement of human gene therapy. However, the use of viral vectors raises many safety concerns and most non-viral methods are less efficient for gene transfer. One of the breakthroughs in vector technology is the combination of the vector with various polymers. HVJ (hemagglutinating virus of Japan) envelope vector (HVJ-E) has been developed as a versatile gene transfer vector. In this study, we combined HVJ-E with cationized gelatin to make it a more powerful tool and assessed its transfection efficiency in vitro and in vivo. In addition, we investigated the mechanism of the gene transfer by means of the inhibition of fusion or endocytosis. The combination of both protamine sulfate and cationized gelatin with HVJ-E, referred to as PS-CG-HVJ-E, further enhanced the in vitro transfection efficiency. In CT26 cells, the luciferase gene expression of PS-CG-HVJ-E was approximately 10 times higher than that of the combination of protamine sulfate with HVJ-E or the combination of cationized gelatin with HVJ-E, referred to as PS-HVJ-E or CG-HVJ-E, respectively. Furthermore, the luciferase gene expression in liver mediated by intravenous administration of CG-HVJ-E was much higher than the luciferase gene expression mediated by PS-HVJ-E or PS-CG-HVJ-E and approximately 100 times higher than that mediated by HVJ-E alone. Cationized gelatin-conjugated HVJ-E enhanced gene transfection efficiency both in vitro and in vivo. These results suggest that low molecular weight cationized gelatin may be appropriate for complex formation with various envelope viruses, such as retrovirus, herpes virus and HIV.
    The Journal of Gene Medicine 08/2005; 7(7):888-97. · 2.16 Impact Factor
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    [Show abstract] [Hide abstract]
    ABSTRACT: Vector development is critical for the advancement of human gene therapy. However, the use of viral vectors raises many safety concerns and most non-viral methods are less efficient for gene transfer. One of the breakthroughs in vector technology is the combination of the vector with various polymers. HVJ (hemagglutinating virus of Japan) envelope vector (HVJ-E) has been developed as a versatile gene transfer vector. In this study, we combined HVJ-E with cationized gelatin(CG) to make it a more powerful tool and assessed its transfection efficiency in vitro and in vivo. CG is one of the most suitable polymers for the complex formation with HVJ-E because of the positive charge and biocompatibility. As shown in Fig. 1, we combined it with HVJ-E and used it in vitro and in vivo experiments. In addition, we investigated the mechanism of the gene transfer by means of the inhibition of fusion or endocytosis. The combination of both protamine sulfate(PS) and CG with HVJ-E, referred to as PS-CG-HVJ-E, further enhanced the in vitro transfection efficiency. In CT26 cells, the luciferase gene expression of PS-CG-HVJ-E was approximately 10 times higher than that of the combination of PS with HVJ-E or the combination of CG with HVJ-E, referred to as PS-HVJ-E or CG-HVJ-E, respectively. In case of in vivo study, we tried intravenous administration at first. In conclusion, the luciferase gene expression in liver mediated by intravenous administration of CG-HVJ-E was much higher than the luciferase gene expression mediated by PS-HVJ-E or PS-CG-HVJ-E and approximately 100 times higher than that mediated by HVJ-E alone. Next, we tried intraperitoneal administration of CG-HVJ-E containing luciferase gene to the peritoneal disseminated colon tumor model mice. As shown in Fig. 2, the luciferase gene expression was specifically detected at tumor nodules. Thus, cationized gelatin-conjugated HVJ-E enhanced gene transfection efficiency both in vitro and in vivo. These results suggest that the conjugation with low molecular weight cationized gelatin may increase in vivo transfection efficiency of various recombinant viral vectors such as retrovirus, herpes virus and lentivirus vector.
    Molecular Therapy 05/2005; · 7.04 Impact Factor

Publication Stats

33 Citations
14.80 Total Impact Points

Institutions

  • 2005–2006
    • Osaka University
      • Division of Gene Therapy Science
      Ōsaka-shi, Osaka-fu, Japan