Hydrodynamic Gene Delivery to Non-human Primates

• Project/Area Number: 26860354
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Niigata University
• Principal Investigator: KAMIMURA KENYA 新潟大学, 医歯学系, 助教 (00579146)
• Research Collaborator: Terai Shuji 新潟大学, 医歯学系, 教授 ; Aoyagi Yutaka 新潟医療センター, 消化器病センター長 ; Suda Takeshi 新潟大学, 医歯学総合病院, 特任教授 ; Yokoo Takeshi 新潟大学, 医歯学総合研究科, 客員研究員 ; Fujisawa Nobuyoshi 新潟大学, 脳研究所, 助教 ; Yoshida Hidenori 新潟大学, 医歯学系, 助教 ; Oda Masafumi 新潟大学, 地域創生推進機構, 教授 ; Liu Dexi ジョージア大学, 教授
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 遺伝子治療 / 肝臓特異的遺伝子導入 / ハイドロダイナミック遺伝子導入法 / 核酸医薬 / ドラッグデリバリー / 肝臓 / 非ウイルスベクター / 大動物 / 血管造影手技 / 血友病

Outline of Final Research Achievements

gene therapy. We have previously reported the effectiveness of image-guided liver-lobe specific hydrodynamic gene delivery. Here, we have assessed the efficiency and the safety of the procedure in non-human primates in this study. The injection catheter was inserted in the lobular hepatic veins and the hydrodynamic injection of the marker plasmid DNA was performed with a various parameters including, injection pressure, volume, flow rate, etc. Based on the results obtained, the optimum parameters were defined followed by the long-term gene expression study using the parameters injecting plasmid expressing human factor IX DNA. The efficiency and safety of the procedure have been confirmed and the development of the gene delivery system and the pre-clinical study are ongoing research programs.

Research Products

• [Int'l Joint Research] University of Georgia/University of North Carolina(米国)
• [Journal Article] Effects of fibrotic tissue on liver-targeted hydrodynamic gene delivery. (2016)
  • Author(s): Kobayashi Y, Kamimura K, Abe H, Yokoo T, Ogawa K, Shinagawa Y, Goto R, Inoue R, Ohtsuka M, Miura H, Kanefuji T, Suda T, Tsuchida M, Aoyagi Y, Zhang G, Liu D, Terai S.
  • Journal Title: Mol Ther Nucleic Acids Volume: . 5: e359. Pages: 1-8
  • DOI: 10.1038/mtna.2016.63
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Liver-targeted Hydrodynamic Gene Therapy: Recent Advances in the Technique. (2016)
  • Author(s): Yokoo T, Kamimura K, Abe H, Kobayashi Y, Kanefuji T, Ogawa K, Goto R, Suda T, Oda M, and Terai S.
  • Journal Title: World J Gastroenterol Volume: 22: Issue: 40 Pages: 8862-8868
  • DOI: 10.3748/wjg.v22.i40.8862
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effective prevention of liver fibrosis by liver-targeted hydrodynamic gene delivery of matrix metalloproteinase-13 in a rat liver fibrosis model. (2016)
  • Author(s): Abe H, Kamimura K, Kobayashi Y, Ohtsuka M, Miura H, Ohashi R, Yokoo T, Kanefuji T, Suda T, Tsuchida M, Aoyagi Y, Zhang G, Liu D, Terai S.
  • Journal Title: Mol Ther Nucleic Acids Volume: 5 Pages: e276-e276
  • DOI: 10.1038/mtna.2015.49
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Image-guided hydrodynamic gene delivery: Current status and future directions. (2015)
  • Author(s): Kamimura K, Yokoo T, Abe H, Kobayashi Y, Ogawa K, Shinagawa Y, Inoue R, Terai S.
  • Journal Title: Pharmaceutics Volume: 7 Issue: 3 Pages: 213-223
  • DOI: 10.3390/pharmaceutics7030213
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Site-specific impact of a regional hydrodynamic injection: computed tomography study during hydrodynamic injection targeting the swine liver. (2015)
  • Author(s): Yokoo T, Kanefuji T, Suda T, Kamimura K, Liu D, Terai S
  • Journal Title: Pharmaceutics Volume: 7 Issue: 3 Pages: 334-343
  • DOI: 10.3390/pharmaceutics7030334
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Safety assessment of liver-targeted hydrodynamic gene delivery in dogs. (2014)
  • Author(s): Kamimura K, Kanefuji T, Yokoo T, Abe H, Suda T, Kobayashi Y, Zhang G, Aoyagi Y, Liu D.
  • Journal Title: PLoS One. Volume: 9 Issue: 9 Pages: e107203-e107203
  • DOI: 10.1371/journal.pone.0107203
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gene Therapy for Liver Fibrosis. (2014)
  • Author(s): Abe H, Kamimura K, Yokoo T, Suda T, Kobayashi Y, Aoyagi Y
  • Journal Title: JSM Gastroenterol Hepatol Volume: 2(3) Pages: 1028-1028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hemodynamics of a hydrodynamic injection. (2014)
  • Author(s): Kanefuji T, Yokoo T, Suda T, Abe H, Kamimura K, Liu D.
  • Journal Title: Mol Ther Methods&Clinical Development Volume: 1 Pages: 14029-14029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Development of Image-guided, Liver Lobe-specific Hydrodynamic Gene Delivery Method for Gene Therapy in Liver Diseases (2016)
  • Author(s): Kenya Kamimura
  • Organizer: Annual Meeting of American Association for the Study of Liver Diseases 2016
  • Place of Presentation: John B Hynes Veterabs N\Memorial Convention Center, Boston, MA, USA
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] Therapeutic Effect of Liver-targeted Hydrodynamic Delivery of MMP13 Gene on Liver Fibrosis (2016)
  • Author(s): Kenya Kamimura
  • Organizer: 第22回日本遺伝子治療学会
  • Place of Presentation: 虎ノ門ヒルズ（東京都、港区）
  • Year and Date: 2016-07-28
  • Int'l Joint Research
• [Presentation] 臓器特異的ハイドロダイナミック遺伝子導入法による肝疾患の遺伝子治療 (2016)
  • Author(s): 上村顕也
  • Organizer: 102回 日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都、新宿区）
  • Year and Date: 2016-04-21
• [Presentation] Development of Effective Gene Therapy for Liver Fibrosis (2016)
  • Author(s): Kenya Kamimura, Hiroyuki Abe, Yuji Kobayashi, Takeshi Yokoo, Masato Ohtsuka, Hiromi Miura, Yoko Shinagawa, Kohei Ogawa, Hirokazu Kawai, Satoshi Yamagiwa, and Shuji Terai
  • Organizer: 第25回 Asian Pacific Association for the Study of the Liver
  • Place of Presentation: グランドプリンスホテル新高輪 （東京都品川区）
  • Year and Date: 2016-02-22
  • Int'l Joint Research
• [Presentation] ハイドロダイナミック細胞内遺伝子送達システムの開発 (2015)
  • Author(s): 上村顕也・阿部寛幸・小林雄司・横尾健・須田剛士・上村博輝・土屋淳紀・高村昌昭・川合弘一・山際訓・寺井崇二
  • Organizer: 第19回日本肝臓学会大会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都品川区）
  • Year and Date: 2015-10-08
• [Presentation] The Effect of Fibrosis on Gene Delivery Efficiency of Hydrodynamics-based Gene Delivery (2015)
  • Author(s): Kenya Kamimura, Hiroyuki Abe, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Takeshi Yokoo, Takeshi Suda, Masanori Tsuchida, Dexi Liu, and Shuji Terai
  • Organizer: 第21回日本遺伝子治療学会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-07-24
  • Int'l Joint Research
• [Presentation] Image-guided, Liver-targeted Hydrodynamic Gene Delivery in Dogs - Preclinical Assessment of Effectiveness and Safety of the Procedure (2015)
  • Author(s): Kenya Kamimura, Hiroyuki Abe, Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Yuji Kobayashi, Guisheng Zhang, Masafumi Oda, Yutaka Aoyagi, Shuji Terai, and Dexi Liu
  • Organizer: American Society of Gene and Cell Therapy 18th Annual Meeting
  • Place of Presentation: Hyatt Regency New Orleans, LA, USA
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in Rat Liver Fibrosis Model (2015)
  • Author(s): Hiroyuki Abe, Kenya Kamimura, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Riuko Ohashi, Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, and Shuji Terai
  • Organizer: American Society of Gene and Cell Therapy 18th Annual Meeting
  • Place of Presentation: Hyatt Regency New Orleans, LA, USA
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] Effect of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery (2015)
  • Author(s): Yuji Kobayashi1, Kenya Kamimura, Hiroyuki Abe, Masato Ohtsuka, Hiromi Miura, Takeshi Yokoo, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Dexi Liu, and Shuji Terai
  • Organizer: American Society of Gene and Cell Therapy 18th Annual Meeting
  • Place of Presentation: Hyatt Regency New Orleans, LA, USA
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] 新規ハイドロダイナミック遺伝子導入システムの有用性と安全性の検証―ハイドロダイナミック法の臨床試験へ向けて― (2015)
  • Author(s): 上村顕也、阿部寛幸、横尾 健、Liu Dexi、尾田雅文、寺井崇二
  • Organizer: 第１５回遺伝子デリバリー研究会
  • Place of Presentation: 京都薬科大学 愛学館3階 愛学ホール（京都府京都市）
  • Year and Date: 2015-05-01
• [Presentation] ハイドロダイナミック遺伝子導入法によるラット肝硬変モデルの遺伝子治療 (2014)
  • Author(s): 阿部寛幸，上村顕也，大塚正人，横尾健，三浦浩美，兼藤努，須田剛士，青柳豊
  • Organizer: 第56回 日本消化器病学会大会
  • Place of Presentation: ポートアイランド、神戸
  • Year and Date: 2014-10-24
• [Presentation] Hydrodynamics-based Gene Delivery to the Fibrotic Liver (2014)
  • Author(s): Kamimura K, et al.
  • Organizer: 第20回日本遺伝子治療学会
  • Place of Presentation: 慈恵医大講堂、東京
  • Year and Date: 2014-08-06 – 2014-08-08
• [Presentation] Parameters for Optimal Hydrodynamic Gene Delivery to Pig Liver Using an Image-guided and Lobe-specific Procedure (2014)
  • Author(s): Kamimura K, et al.
  • Organizer: The American Society of Gene & Cell Therapy 17th Annual Meeting
  • Place of Presentation: Marriott Wardman Park, Wahington DC, USA
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Overexpression of Matrix Metalloproteinase-13 Gene by the Method of Hydrodynamic Gene Delivery Prevents Liver Fibrosis in Rats (2014)
  • Author(s): Abe H, Kamimura K, et al.
  • Organizer: The American Society of Gene & Cell Therapy 17th Annual Meeting
  • Place of Presentation: Marriott Wardman Park, Wahington DC, USA
  • Year and Date: 2014-05-21 – 2014-05-24
• [Book] Image-Guided Hydrodynamic Gene Delivery to the Liver: Toward Clinical Applications (2016)
  • Author(s): Kamimura K, Suda T, Kanefuji T, Yokoo T, Abe H, Kobayashi Y, Aoyagi Y, Liu D
  • Total Pages: 185
  • Publisher: Springer Japan
• [Book] Advances and Challenges in the Delivery of Nucleic Acid Therapies, 2015 Ch 8, Hydrodynamic Gene Delivery (2015)
  • Author(s): Kamimura K, Suda T, Liu D
  • Total Pages: 128
  • Publisher: Future Science