Retrograde injection of plasmid DNA containing nano bubble via pulmonary vien

• Project/Area Number: 24592084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Niigata University
• Principal Investigator: TSUCHIDA MASANORI 新潟大学, 医歯学系, 教授 (60293221)
• Co-Investigator(Kenkyū-buntansha): KOIKE TERUMOTO 新潟大学, 医歯学系, 講師 (90635723)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 遺伝子導入 / プラスミドベクター / 肺静脈 / 逆行性投与 / ナノバブル / 逆行性 / 逆行性導入 / 肺

Outline of Final Research Achievements

Lung-targeted gene transfer is expected to revolutionize the treatment of respiratory diseases. In this study, we demonstrated that naked plasmid deoxyribonucleic acid (DNA) can be transferred into alveolar cells in normal rats, by retrograde injection into the pulmonary vein with the left pulmonary artery clamped. When a lusiferase expression plasmid vector pCAGGS-lusiferase in a reporter assay was examined, the maximal lusiferase expression was obtained when the DNA solution was injected within 30 s in a volume of 1.0 mL. We detected lacZ expression exclusively in the type II pnumocyte attached to alveolar walls by immunoelectron microscopy. Protocol for naked plasmid DNA transfer into rat lung using this hydrodynamics-based transfection method was established. However, addition of micro babble did not enhance the efficacy of gene transfer. On the other hand, micro babble enhanced the efficacy of gene transfer via antegrade injection.

Research Products

• [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
• [Presentation] The Effect of Fibrosis on Gene Delivery Efficiency of Hydrodynamics-based Gene Delivery (2015)
  • Author(s): Kamimura K Abe H, Kobayashi Y, Ohtsuka M, Miura H, Yokoo T, Suda T, Tsuchida M, Liu D, Terai S
  • Organizer: 第21回日本遺伝子治療学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-07-25
• [Presentation] Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in Rat Liver Fibrosis Model (2015)
  • 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
  • Organizer: 18th Annual Meeting of American Society of Gene & Cell Therapy
  • Place of Presentation: U.S.A, New Orleans, LA
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] Effect of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery (2015)
  • Author(s): Kobayashi Y, Kamimura K, Abe H, Ohtsuka M, Miura H, Yokoo T, Suda T, Tsuchida M, Aoyagi Y, Liu D, Terai S
  • Organizer: 18th Annual Meeting of American Society of Gene & Cell Therapy
  • Place of Presentation: U.S.A, New Orleans, LA
  • Year and Date: 2015-05-13
  • Int'l Joint Research