The development of in vivo gene delivery systems to peritoneum to inhibit peritoneal fibrosis

• Project/Area Number: 25461252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Jichi Medical University
• Principal Investigator: Morishita Yoshiyuki 自治医科大学, 医学部, 教授 (30570494)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腹膜線維症 / 遺伝子治療 / ドラッグデリバリー / スモールRNA / デリバリー / マイクロRNA / バイオマーカー

Outline of Final Research Achievements

1.We developed an in vivo siRNA delivery system with liposome based nanoparticles (NPs) to peritoneum to inhibit peritoneal fibrosis. TGF-β1-siRNAs encapsulated in NPs (TGF-β1-siRNAs-NPs) dissolved in peritoenal dialsysis (PD) fluid were intraperitoneally injected into the peritoneal fibrosis (PF) mice. They significantly knocked down TGF-β1 expression in peritoneum and inhibited peritoneal thickness with fibrous change.

2. We identified microRNA(miRNA)-21-5p inhibition by anti-miRNA-21-5p-LNA is effective for the prevention of PF. We also identified that sevreal microRNAs (miRNA-21-5p, miRNA-221-3p, miRNA-34a-5p and miRNA-327) may be useful as novel diagnostic biomarkers for PF.

Research Products

• [Journal Article] MicroRNA expression profiling in peritoneal fibrosis. (2016)
  • Author(s): Morishita Y, Yoshizawa H, Watanabe M, Imai R, Imai T, Hirahara I, Akimoto T, Ookawara S, Muto S, Nagata D.
  • Journal Title: Transl Res Volume: 169 Pages: 47-66
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] スモールRNAデリバリーによる腎・腹膜線維化抑制 (2016)
  • Author(s): 森下義幸
  • Journal Title: 腎と透析 Volume: ８０ Pages: 415-422
• [Journal Article] TGF-β₁-siRNA delivery with nanoparticles inhibits peritoneal fibrosis. (2015)
  • Author(s): Yoshizawa H, Morishita Y, Watanabe M, Ishibashi K, Muto S, Kusano E, Nagata D
  • Journal Title: Gene Ther Volume: 22 Pages: 333-340
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TGF-β1-siRNA delivery with nanoparticles inhibits peritoneal fibrosis. (2015)
  • Author(s): Yoshizawa H, Morishita Y, Watanabe M, Ishibashi K, Muto S, Kusano E, Nagata D
  • Journal Title: Gene Therapy Volume: ２２ Issue: 4 Pages: 333-340
  • DOI: 10.1038/gt.2014.116
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 腹膜線維症を調節するmicroRNAの解析-治療ターゲットおよび新規バイオマーカーとしての可能性- (2016)
  • Author(s): 森下義幸
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-17
• [Presentation] MicroRNA Expression Profiling in Peritoneal Fibrosis (2015)
  • Author(s): Yoshiyuki Morishita
  • Organizer: ASN Kidney Week 2015
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Nanoparticle を担体とした siRNA デリバリーシ (2014)
  • Author(s): 吉澤寛道、森下義幸、渡辺南、武藤重明、長田太助
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] The Development Of In Vivo Small Interfering RNA Delivery System with Nanoparticles to Peritoneum for the Treatment Of Peritoneal Fibrosis (2013)
  • Author(s): Hiromichi Yoshizawa, Yoshiyuki Morishita, Akira Onishi, Minami Watanabe, Shigeaki Muto and Eiji Kusano
  • Organizer: American Society of Nephrology, Kidney Week 2013 Annual Meeting
  • Place of Presentation: Atlanta, USA