The study of clinical application for HCV with miRNA containing the modified exosomes derived from iPS cells

• Project/Area Number: 23590993
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical University
• Principal Investigator: TAKANASHI Masakatsu 東京医科大学, 医学部, 講師 (80312007)
• Co-Investigator(Kenkyū-buntansha): MURAKAMI Yoshiki 大阪市立大学, 医学(系)研究科(研究院), 准教授 (00397556) ; UMEZAWA Akihiro 独立行政法人国立成育医療研究センター, 部長 (70213486)
• Co-Investigator(Renkei-kenkyūsha): SUDO Katsuko 東京医科大学, 医学部, 兼任講師 (50126091)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: エクソソーム / HCV / 分子標的治療 / exosome / microRNA

Research Abstract

It is necessary to develop drug delivery system (DDS) to give a treatment using miRNA which targets HCV. In this study we examined to apply exosome to DDS for miRNA. We purified the exosomes from the cells which produced GE11 with the partial aliment of the ligand for EGFR and gave the target cell specificity. We produced the exosomes contain miRNA to gene transfer into the exosome-producing cells and confirmed that it was included in purified exosomes. We confirmed that the exosomes specifically performed delivery to the xenografted human cancer cells in mice. So we showed possibility to apply to treatment of the HCV by the exosomes containing miRNA which targets HCV in this system.

Research Products

• [Journal Article] miRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis (2013)
  • Author(s): Wu W., Takanashi M., Borjiigin N., Ohno S., Fujita K., Hoshino S., Osaka Y., Tsuchida A., Kuroda M.
  • Journal Title: British J. Cancer Volume: 108(3) Pages: 653-661
  • Peer Reviewed
• [Journal Article] MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis. (2013)
  • Author(s): Wu W, Takanashi M, Borjigin N, Ohno SI, Fujita K, Hoshino S, Osaka Y, Tsuchida A, Kuroda M.
  • Journal Title: Br J Cancer Volume: 108(3) Issue: 3 Pages: 653-661
  • DOI: 10.1038/bjc.2012.587
  • Peer Reviewed
• [Journal Article] Isolation of mRNAs that target EGFR mRNA in human lung cancer (2012)
  • Author(s): Yamaguchi G, Takanashi M., Fujita K., Ohira T., Kuroda M., Ikeda N.
  • Journal Title: Biochem Biophys Res Commun Volume: 420(2) Pages: 411-416
  • Peer Reviewed
• [Journal Article] Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells (2012)
  • Author(s): Ohno S., Takanashi M., Sudo K., Ueda S., Ishida A., Matsuyama N., Fujita K., Mizitani T., Ohgi T., Ochiya T., et. al.
  • Journal Title: Mol. Ther Volume: 21(1) Pages: 185-191
  • Peer Reviewed
• [Journal Article] TLS-CHOP represses miR-486 expression, inducing upregulation of a metastasis regulator PAI-1 in human myxoid liposarcoma (2012)
  • Author(s): Borjigin N., Ohno S., Wu W., Tanaka M., Suzuki R., Fujita K., Takanashi M., Oikawa K., et. al.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 427(2) Pages: 355-360
  • Peer Reviewed
• [Journal Article] A novel oncogenic pathway by TLS- CHOP involving repression of MDA-7/ IL-24 expression (2012)
  • Author(s): Oikawa K., Tanaka S., Itoh S., Takanashi M., Ozaki T., Muragaki Y., Kuroda M.
  • Journal Title: British J. Canc Volume: 106(12) Pages: 1976-1979
  • Peer Reviewed
• [Journal Article] Identification of a novel role of Septin 10 in paclitaxel-resistance in cancers through a functional genomics screen (2012)
  • Author(s): Xu M., Takanashi M., Oikawa K., Nishi H., Isaka K., Yoshimoto T., Ohyashiki J., Kuroda M.
  • Journal Title: Cancer Sci Volume: 103(4) Pages: 821-827
  • Peer Reviewed
• [Journal Article] Systemically injected exosomes targeted to EGFR deliver anti-tumor microRNA to breast cancer cells (2012)
  • Author(s): 後藤 典子
  • Journal Title: Molecular Therapy Volume: 21 Issue: 1 Pages: 185-191
  • DOI: 10.1038/mt.2012.180
  • Peer Reviewed
• [Journal Article] TLS-CHOP represses miR-486 expression, inducing upregulation of a metastasis regulator PAI-1 in human myxoid liposarcoma (2012)
  • Author(s): N. Borjigin, S. Ohno, W. Wu, M. Tanaka, R. Suzuki, K. Fujita, M. Takanashi, K. Oikawa, T. Goto, T. Motoi, T. Kosaka, K. Yamamoto, M. Kuroda
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 427 Issue: 2 Pages: 355-360
  • DOI: 10.1016/j.bbrc.2012.09.063
  • Peer Reviewed
• [Journal Article] A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24 expression (2012)
  • Author(s): K. Oikawa, M. Tanaka, S. Itoh, M. Takanashi, T. Ozaki, Y. Muragaki, M. Kuroda
  • Journal Title: Br. J. Cancer Volume: 106 Issue: 12 Pages: 1976-1979
  • DOI: 10.1038/bjc.2012.199
  • Peer Reviewed
• [Journal Article] Isolation of miRNAs that target EGFR mRNA in human lung cancer (2012)
  • Author(s): Yamaguchi G, Takanashi M, Tanaka M, Fujita K, Ohira T, Kuroda M, Ikeda N
  • Journal Title: Biochem Biophys Res Commun Volume: 420(2) Issue: 2 Pages: 411-6
  • DOI: 10.1016/j.bbrc.2012.03.008
  • Peer Reviewed
• [Journal Article] Identification of a novel role of Septin 10 in Paclitaxel-resistance in cancers through a functional genomics screen (2012)
  • Author(s): Xu M, Takanashi M, Oikawa K, Nishi H, Isaka K, Yoshimoto T, Ohyashiki J, Kuroda M
  • Journal Title: Cancer Sci Volume: 103 Issue: 4 Pages: 821-827
  • DOI: 10.1111/j.1349-7006.2012.02221.x
  • Peer Reviewed
• [Journal Article] Isolation of miRNAs that target EGFR mRNA in human lung cancer. (2012)
  • Author(s): Yamaguchi G, Takanashi M, Tanaka M, Fujita K, Ohira T, Kuroda M, Ikeda N.
  • Journal Title: Biochem Biophys Res Commun. Volume: 420 (2) Pages: 411-416
  • Peer Reviewed
• [Journal Article] miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer (2011)
  • Author(s): Tsuchida A., Ohno S., Wu W., Borjigin N., Fujita K., Aoki T., Ueda S., Takanashi M., Kuroda M.
  • Journal Title: Cancer Sci Volume: 102(12) Pages: 2264-2271
  • NAID: 10030246362
  • Peer Reviewed
• [Journal Article] Anthocyanidins-enriched bilberry extracts finhibit 3T3-L1 adipocyte differentiation via the insulin pathway (2011)
  • Author(s): Suzuki R., Tanaka M., Takanashi M., Hussain A., Yuan B., Toyoda H., Kuroda M.
  • Journal Title: Nutrition & metabolism Volume: 8 Pages: 14-14
  • Peer Reviewed
• [Journal Article] miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer. (2011)
  • Author(s): Akihiko Tsuchida, Shinichiro Ohno, Weihong Wu, Nariso Borjigin, Koji Fujita, Tastuya Aoki, Shinobu Ueda, Masakatsu Takanashi, Masahiko Kuroda
  • Journal Title: Cancer science Volume: 102 (12) Pages: 2264-2271
  • NAID: 10030246362
  • Peer Reviewed
• [Journal Article] Anthocyanidins-enriched bilberry extracts inhibit 3T3-L1 adipocyte differentiation via the insulin pathway. (2011)
  • Author(s): Rieko Suzuki, Masami Tanaka, Masakatsu Takanashi, Aashiq Hussain, Bo Yuan, Hiroo Toyoda, Masahiko Kuroda
  • Journal Title: Nutrition & metabolism Volume: 8 Pages: 14-14
  • Peer Reviewed
• [Presentation] 新規核酸を用いた血管新生網膜症に対する分子標的治療薬 (2013)
  • Author(s): 高梨正勝須藤カツ子松永芳径石川章夫大木忠明濱崎智洋後藤浩黒田雅彦
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 札幌
• [Presentation] Systemically injected exosomes targeted to EGFR deliver anti-tumor microRNA to breast cancer cells (2013)
  • Author(s): Ohno S, Takanashi M, Ohgi T, Mizutani T, Murakami T, Kuroda M.
  • Organizer: Keystones Symposia Conference-Noncording RNAs in Development and cancer
  • Place of Presentation: Vancouver, CANADA
• [Presentation] 新規核酸を用いた血管新生網膜症に対する分子標的治療法の開発 (2013)
  • Author(s): 髙梨正勝 須藤カツ子 松永芳径 石川章夫 大木忠明 濱崎智洋 後藤浩 黒田雅彦
  • Organizer: 第102回日本病理学会
  • Place of Presentation: 札幌
• [Presentation] Systemically injected exosomes targeted to EGFR deliver anti-tumor microRNA to breast cancer cells. (2013)
  • Author(s): Shinichiro Ohno, Masakatsu Takanashi, Tadaaki Ohgi, Takayuki Mizutani, Yoshiki Murakami, Masahiko Kuroda
  • Organizer: Keystone Symposia Conference - Noncoding RNAs in Development and Cancer(A7)
  • Place of Presentation: Vancouver, British Columbia, CANADA
• [Presentation] 新規核酸を用いた血管新生網膜症に対する分子標的治療法の開発 (2012)
  • Author(s): 高梨正勝須藤カツ子松永芳径石川章夫大木忠明濱崎智洋後藤浩黒田雅彦
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
• [Presentation] Wapl regulates HP1 expression and levels of various histone H3 tail modification (2012)
  • Author(s): Oikawa K Takanashi M Niwa M Sun Y Gui T Shimokado A Itoh S Ozaki T Kuroda M Muragaki Y.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] マウスに経口投与したエクソソームの生体内での安定性と分布 (2012)
  • Author(s): 高梨正勝須藤カツ子大野慎一郎上田しのぶ石川章夫黒田雅彦
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 粘膜型脂肪肉腫においてTLS-CHOPは抗がん性サイトカインMDA-7/IL-24の発現を抑制する (2012)
  • Author(s): 及川恒輔高梨正勝黒田雅彦村垣泰光
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] (2012)
  • Author(s): 高梨正勝須藤カツ子松永芳径大木忠明濱崎智洋谷口維紹臼井嘉彦後藤浩黒田雅彦
  • Organizer: 第32回日本眼薬理学会総会
  • Place of Presentation: 滋賀
• [Presentation] TLS-CHOP癌遺伝子が発現制御するmiRNAの解析 (2012)
  • Author(s): 那日蘇大野慎一郎田中正視呉偉紅田中理英子藤田浩司高梨正勝黒田雅彦
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] 胃低分化癌におけるin situ hybridization法を用いたmiR-92aおよびmiR-200cの発現低下の意義 (2012)
  • Author(s): 倉田厚呉偉紅山田正俊那日蘇藤田浩司大野慎一郎高梨正勝黒田雅彦
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] Wapl regulates HP1 expression and levels of various histone H3 tail modifications. (2012)
  • Author(s): Kosuke Oikawa, Masakatsu Takanashi, Mayako Niwa, Yujing Sun, Ting Gui, Aiko Shimokado, Shunji Itoh, Takashi Ozaki, Masahiko Kuroda, Yasuteru Muragaki.
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] 粘液型脂肪肉腫においてTLS-CHOPは抗がん性サイトカインMDA-7/IL24の発現を抑制する． (2012)
  • Author(s): 及川 恒輔、髙梨 正勝、黒田 雅彦、村垣 泰光
  • Organizer: 71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 血管新生網膜症に対する分子標的治療法を目指した核酸薬の開発． (2012)
  • Author(s): 髙梨 正勝、須藤 カツ子、松永 芳径、大木 忠明、濱崎 智洋、谷口 維紹、仲矢 丈雄、臼井 嘉彦、後藤 浩、黒田 雅彦
  • Organizer: 第32回日本眼薬理学会
  • Place of Presentation: 滋賀
• [Presentation] 胃低分化癌におけるin situ hybridization法を用いたmiRNA-92aおよび200cの発現低下の意義 (2012)
  • Author(s): 倉田 厚、呉 偉紅、山田 正俊、那 日蘇、藤田 浩司、大野 慎一郎、高梨 正勝、黒田 雅彦
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] TLS-CHOPがん遺伝子が発現制御するmiRNAの解析 (2012)
  • Author(s): ボルジゲン 那日蘇、大野 慎一郎、田中 正視、呉 偉紅、田中 理英子、藤田 浩司、高梨 正勝、黒田 雅彦
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] EGFRリガンド発現エクソソームを用いた新規ドラッグデリバリーシステムの開発 (2012)
  • Author(s): 大野 慎一郎、上田 しのぶ、石川 章夫、松山 永久、藤田 浩司、高梨 正勝、黒田 雅彦
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] Novel type of small RNA exhibit RNA interference effect without activation of Toll-like receptor 3 (2012)
  • Author(s): Masakatsu Takanashi, Shinichiro Ohno, Tadaaki Ohgi, Kazunori Yoshikawa, Hirotake Hayashi , Takayuki Mizutani, Masahiko Kuroda
  • Organizer: Keystone symposia Nucleic Acid Therapeutics: From Base Pairs to Bedsides (A2)
  • Place of Presentation: Santa Fe, New Mexico, USA
• [Presentation] Selective target delivery of miRNA using EGF expressing exosomes (2012)
  • Author(s): Shinichiro Ohno, Masakatsu Takanashi, Shinobu Ueda, Tadaaki Ohgi, Takayuki Mizutani, Masahiko Kuroda
  • Organizer: Keystone symposia Nucleic Acid Therapeutics: From Base Pairs to Bedsides (A2)
  • Place of Presentation: Santa Fe, New Mexico, USA
• [Presentation] 人工型exosomeの生体分布と安定性についての研究 (2011)
  • Author(s): 高梨正勝須藤カツ子大野慎一郎上田しのぶ石川章夫黒田雅彦
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
• [Presentation] CD63-GFPを発現したエクソソームのマウス生体内での安定性と分布について (2011)
  • Author(s): 高梨正勝須藤カツ子大野慎一郎上田しのぶ石川章夫黒田雅彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 人工型exosomeの生体内分布と安定性についての研究 (2011)
  • Author(s): 高梨 正勝、須藤 カツ子、大野 慎一郎、上田 しのぶ、石川 章夫、黒田 雅彦
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
• [Presentation] リガンド修飾エクソソームによるEGF receptor発現細胞を標的としたドラッグデリバリーシステムの開発 (2011)
  • Author(s): 大野 慎一郎、上田 しのぶ、石川 章夫、松山 永久、高梨 正勝、黒田 雅彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 乳がん幹細胞の維持に関与するmicroRNAの探索 (2011)
  • Author(s): 上田 しのぶ、高梨 正勝、黒田 雅彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] "Delivery of antitumor molecules to the EGFR expressing cancer using EGF expressing exosomes (2011)
  • Author(s): 大野 慎一郎、上田 しのぶ、石川 章夫、藤田 浩司、高梨 正勝、黒田 雅彦
  • Organizer: 第３７回分子生物学会年会
  • Place of Presentation: 横浜