Development of hydrodynamic gene delivery system for the delivery to the mitochondria

• Project/Area Number: 24590961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Niigata University
• Principal Investigator: SUDA Takeshi 新潟大学, 医歯学総合病院, 講師 (10361916)
• Co-Investigator(Kenkyū-buntansha): ODA Masafumi 新潟大学, 産学地域連携推進機構, 教授 (80372473)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ミトコンドリア / 遺伝子治療 / ハイドロダイナミック導入法 / レオロジー / ハイドロダイナミック遺伝子導入法 / ハイドロダイナミック

Outline of Final Research Achievements

Toward the development of a feasible mitochondrial gene therapy in clinic, the plasmids consist of a mitochondria-specific promotor and terminal signal with genes, which are modified for a mitochondria-specific codon usage, were developed, and we confirmed no expression from the plasmids in the nucleus using a confocal microscopy.
Because hydrodynamic gene delivery could not efficiently deliver the plasmids to mitochondria, proteins binding to the mitochondrial localization signal were employed for enhancing the delivery. In order to prevent the dissociation between the localization signal and proteins, we newly developed hydrodynamic gene delivery injecting a half volume with a half speed of the authentic hydrodynamic delivery.
Now we are evaluating the effectiveness of the modified hydrodynamic system in the delivery of the plasmids to the mitochondria in mice.

Research Products

• [Journal Article] Hemodynamics of a Hydrodynamic Injection (2014)
  • Author(s): Kanefuji T, Yokoo T, Suda T, Abe H, Kamimura K, and Liu D
  • Journal Title: Mol Ther Meth & Clin Dev Volume: 1 Pages: 1-7
  • DOI: 10.1038/mtm.2014.29
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel electric power-driven hydrodynamic injection system for gene delivery: safety and efficacy of human factor IX delivery in rats. (2013)
  • Author(s): Yokoo T
  • Journal Title: Gene Therapy Volume: - Issue: 8 Pages: 816-823
  • DOI: 10.1038/gt.2013.2
  • Peer Reviewed
• [Presentation] Imaging-guided Hydrodynamic Gene Delivery (2015)
  • Author(s): Takeshi Suda
  • Organizer: 18th Annual Meeting of American Society of Gene and Cell Therapy
  • Place of Presentation: Hyatt Regency, New Orleans, USA
  • Year and Date: 2015-05-15
  • Invited
• [Presentation] Rheological Modification of Hydrodynamic Gene Delivery (2015)
  • Author(s): Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Akiomi Ushida, Tomiichi Hasegawa, Kenya Kamimura, Dexi Liu, Shuji Terai
  • Organizer: 18th Annual Meeting of American Society of Gene and Cell Therapy
  • Place of Presentation: Hyatt Regency, New Orleans, USA
  • Year and Date: 2015-05-14
• [Presentation] Impact of Injection Volume on Hydrodynamic Delivery To the Liver in Mice (2015)
  • Author(s): Tsutomu Kanefuji, Takeshi Yokoo, Takeshi Suda, Kunihiko Sawada, Yoshinori Arai, Hiroyuki Abe, Kenya Kamimura, Dexi Liu, Shuji Terai
  • Organizer: 18th Annual Meeting of American Society of Gene and Cell Therapy
  • Place of Presentation: Hyatt Regency, New Orleans, USA
  • Year and Date: 2015-05-14
• [Presentation] ハイドロダイナミック遺伝子導入法の臨床応用へ向けて ―医工連携による日本発のハイドロダイナミック遺伝子導入システムの開発― (2013)
  • Author(s): 上村顕也、須田剛士、兼藤 努、横尾 健、Liu Dexi、青柳 豊
  • Organizer: 第29回日本DDS学会
  • Place of Presentation: 京都市
• [Presentation] Hydrodynamics-based, Liver-targeted Nonviral Gene Therapy Approach for Monogenic Diseases. (2013)
  • Author(s): Takeshi Suda, Takeshi Yokoo, Kenya Kamimura, Tsutomu Kanefuji, Masafumi Oda, Guisheng Zhang, Dexi Liu, and Yutaka Aoyagi
  • Organizer: 第48回欧州肝臓学会総会
  • Place of Presentation: Amsterdam, Nederland
• [Presentation] 新規ハイドロダイナミック遺伝子導入システムの確立と有用性の検証 (2013)
  • Author(s): 横尾健、上村顕也、須田剛士、兼藤努、尾田雅文、田村康、高村昌昭、五十嵐正人、川合弘一、山際訓、野本実、D.Liu、青柳豊
  • Organizer: 第21回日本消化器病関連週間
  • Place of Presentation: 東京
• [Presentation] Image-guided, Hydrodynamic Gene and Cell Delivery through the Liver: Toward Clinical Applications. (2013)
  • Author(s): Kenya Kamimura, Takeshi Suda, and Yutaka Aoyagi
  • Organizer: 第21回日本消化器病関連週間
  • Place of Presentation: 東京
• [Presentation] Long Term Transgene Expression in Rat Liver Using a Novel Electromotor-Driven Hydrodynamic Gene Injector (2012)
  • Author(s): T Yokoo, K Kamimura, T Suda, T Kanefuji, M Oda, G Zhang, D Liu, Y Aoyagi.
  • Organizer: American Society of Gene & Cell Therapy 15th Annual Meeting
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] 医薬工連携による新規遺伝子導入装置の開発と今後の展開 (2012)
  • Author(s): 上村顕也、須田剛士、横尾 健、兼藤 努、Liu Dexi、尾田雅文、青柳 豊
  • Organizer: 第28回日本DDS学会学術集会
  • Place of Presentation: 札幌
• [Book] Non-Viral Vectors for Gene Therapy. Physical Methods and Medical Translation (2015)
  • Author(s): Takeshi Suda and Dexi Liu
  • Total Pages: 296
  • Publisher: Elsevier Inc.
• [Book] Advanced Textbook on Gene Transfer, Gene Therapy, and Genetic Pharmacology (2014)
  • Author(s): Takeshi Suda, Kenya Kamimura, Guisheng Zhang and Dexi Liu
  • Total Pages: 544
  • Publisher: Imperial College Press