Development of siRNA delivery system using exosome targeting for metastasis organs for cancer metastasis therapeutics

• Project/Area Number: 17K08477
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Fukuoka University
• Principal Investigator: Hazekawa Mai 福岡大学, 薬学部, 助教 (10509186)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: エクソソーム / siRNA / メラノーマ / 転移がん / 指向性 / 集積性 / 接着因子 / 転移 / ドラッグデリバリー / 自家移植 / がん転移

Outline of Final Research Achievements

Exosomes are small membrane vesicles containing functional biomolecules that can be horizontally transferred to recipient cells. It has been known that molecules present on tumor-derived exosomes are ‘addressing’ them to specific organ. The purpose of this study was to prepare siRNA delivery system using exosome derived from autologous serum of melanoma lung metastasis in mice model, which is ‘addressing’ to specific organ. Melanoma lung metastasis model mice were treated with exosome transfected siRNA intravenously after surgical removal of the tumor in the hind limb induced by the subcutaneous injection of B16/BL6. The number of lung metastatic tumor cells of exosome treatment group was significantly decreased compared with control. These results suggested that autologous serum-derived exosomes of melanoma-bearing mice can be used potentially as an efficient siRNA delivery carrier for melanoma lung metastasis targeting.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、核酸キャリア開発において、個別化医療の基盤研究の一つとして、自己の生体由来成分を利用した核酸キャリアの創出を目指し、がん種および転移先がカスタム可能なオーダーメード型システムの構築に成功した。本研究成果の独自性は、自己の生体成分を利用することによる免疫原性の軽減だけでなく、キャリア自体がすでに転移先の臓器を指向し、従来のエクソソームの機能である遠隔の他の細胞にRNAを運び情報を伝える性質を最大限に生かしたキャリア設計から治療戦略にあり、他の研究グループではこれまで実施されてこなかった独自の基盤研究技術開発に至った。

Research Products

• [Journal Article] Developing a model for an siRNA delivery system by cancer implantation into zebrafish circulation (2020)
  • Author(s): Shimada Y, Hazekawa M
  • Journal Title: Methods Mol Biol Volume: 2174 Pages: 263-275
  • DOI: 10.1007/978-1-0716-0759-6_17
  • ISBN: 9781071607589, 9781071607596
  • Peer Reviewed
• [Journal Article] Glypican-3を標的とした核酸医薬を用いた卵巣がん腹膜転移治療の有用性 (2020)
  • Author(s): 櫨川舞
  • Journal Title: Precision Medicine Volume: 3(14) Pages: 71-74
  • Peer Reviewed
• [Journal Article] 自己成分由来エクソソームを用いたがん転移治療のための核酸医薬の開発 (2019)
  • Author(s): 櫨川 舞
  • Journal Title: BIO Clinica Volume: 34 Pages: 55-57
• [Journal Article] がん転移治療のための転移臓器指向性自己血清エクソソーム製剤の有用性 (2019)
  • Author(s): 櫨川 舞
  • Journal Title: Precision Medicine Volume: 2 Pages: 165-167
• [Journal Article] がん転移治療のための転移臓器指向性エクソソーム製剤の開発 (2018)
  • Author(s): 櫨川 舞
  • Journal Title: Medical Science Digest Volume: 44 Pages: 594-595
• [Presentation] Specific recognition for target cells using Fab’-PLGA/siRNA-PLGA mixed micelles (2020)
  • Author(s): Hazekawa M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakashima M
  • Organizer: 7th FIP Pharmaceutical Sciences World Congress (PSWC2020 Virtual)
  • Int'l Joint Research
• [Presentation] Development of siRNA delivery system using exosome derived autologous component in melanoma lung metastasis mice model (2019)
  • Author(s): Hazekawa M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakashima M.
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] Development of siRNA delivery system using exosome derived autologous component in melanoma lung metastasis mice model (2019)
  • Author(s): Hazekawa M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakashima M.
  • Organizer: 第78回日本癌学会学術大会
• [Presentation] メラノーマ転移モデルを用いた自己血清エクソソーム製剤に関する検討 (2018)
  • Author(s): 櫨川舞、西中川拓也、安河内（川久保）友世、中島学
  • Organizer: 日本薬剤学会第33年会
• [Presentation] Autologous serum-derived exosomes to deliver siRNA to melanoma cell in lung metastasis (2018)
  • Author(s): Hazekawa M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakashima M.
  • Organizer: 78th FIP world congress of pharmacy and pharmaceutical sciences
  • Int'l Joint Research
• [Presentation] メラノーマ自然転移モデルを用いた自己血清エクソソーム製剤に関する検討 (2018)
  • Author(s): 櫨川舞、西中川拓也、安河内（川久保）友世、中島学
  • Organizer: 日本薬剤学会
• [Presentation] Autologous serum-derived exosomes to deliver siRNA to melanoma cell in lung metastasis (2018)
  • Author(s): Mai Hazekawa, Takuya Nishinakagawa, Tomoyo Kawakubo-Yasukochi, Manabu Nakashima
  • Organizer: 78th FIP world congress of pharmacy and pharmaceutical sciences
  • Int'l Joint Research
• [Remarks] 福岡大学 薬学部 免疫・分子治療学講座HP
  • URL: https://www.cis.fukuoka-u.ac.jp/~lab00011/index.html
• [Remarks] 福岡大学薬学部免疫・分子治療学研究室ホームページ
  • URL: http://www.pha.fukuoka-u.ac.jp/user/chiryou/web/
• [Patent(Industrial Property Rights)] 医薬組成物及びその製造方法 (2020)
  • Inventor(s): 櫨川舞
  • Industrial Property Rights Holder: 櫨川舞
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-143848
  • Filing Date: 2020