| Project/Area Number |
20015003
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Hokkaido University |
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Principal Investigator |
HARASHIMA Hideyoshi Hokkaido University, 大学院・薬学研究院, 教授 (00183567)
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| Co-Investigator(Kenkyū-buntansha) |
紙谷 浩之 北海道大学, 大学院・薬学研究院, 准教授 (10204629)
山田 勇磨 北海道大学, 大学院・薬学研究院, 助教 (60451431)
畠山 浩人 北海道大学, 大学院・薬学研究院, 特任助教 (70504786)
馬場 嘉信 名古屋大学, 大学院・工学系研究科, 教授 (30183916)
秋田 英万 北海道大学, 大学院・薬学研究院, 助教 (80344472)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2009: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2008: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | がん / 遺伝子治療 / siRNA / ワクチン / MEND / デリバリーシステム / 多機能性エンベロープ型ナノ構造体 / PPD / エンドソーム脱出 / 抗腫瘍効果 |
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| Research Abstract |
In this study, we developed a multifunctional envelope-type nano device (MEND) as a non-viral siRNA delivery system for cancer, which can induce the knockdown of tumor specific genes and anti-tumor effect with no toxicity. First, we measured antigen presentation of OVA encapsulated R8-MEND in dendritic cell (DC). As a result, R8-MEND showed specific MHC class I presentation, although showed low MHC class II presentation. Moreover, mice subcutaneously immunized by R8-MEND were showed significant antitumor effect compared with control mice. Next, we prepared GALA/DMEND encapsulating siRNA core condensed with protamine. To investigate antitumor effects, we immunized DCs which were silenced SOCS1 by GALA/DMEND to mice. As a result, SOCS1- silenced DC significantly suppressed tumor growth compared with control DC. Therefore, we succeeded in enhancing antitumor effect by silencing SOCS1 of DC with GALA/DMEND. For systemic siRNA delivery, HT1080 cells were s.c. inoculated into nude mice. After i.v. injection to tumor-bearing mice, GALA/PEG-MEND exhibited high systemic stability and accumulated in tumor tissue. Target □-actin expression in tumor tissue was knockdowned more than 60% after administration of GALA/PEG-MEND (4mg siRNA/kg), which resulted in suppression of tumor growth (特願2010-39667). Serum level of ALT remained normal value, and body weight was unchanged after i.v. administration of GALA/PEG-MEND. These results suggested that GALA/PEG-MEND should be a valuable siRNA delivery system for in vivo tumor and siRNA therapeutics.
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