The engineering of neuron specific targeted helper-dependent adenovirus vectors for the treatment of neuropathic pain.

• Project/Area Number: 21890109
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: TERASHIMA Tomoya Shiga University of Medical Science, 医学部, 助教 (40378485)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000); Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000); Fiscal Year 2009: ¥1,417,000 (Direct Cost: ¥1,090,000、Indirect Cost: ¥327,000)
• Keywords: ウイルス / バイオテクノロジー / 再生医学 / 脳・神経 / 遺伝子

Research Abstract

(1) We established two stable cell lines, which were 293-cre cells and 293-fiber cells. 293-cre cells continuously expressed cre recombinase, are essential to be produced helper-dependent adenovirus vectors as one of the gutless virus vectors. 293-fiber cells are used to be produced and amplified the helper virus with high affinities against neuronal cells.
(2) We stored much amount of wild type helper virus with 293-cre cells to be produced wild type HDAd.
(3) We stored much amount of DRG targeting helper virus with 293-fiber cells to be produced DRG targeting HDAd.
(4) cDNA of glutamic acid decarboxylase (GAD) was subcloned from cDNA library of mouse brain and inserted into pdelta28 vector with EF-1 promoter for HDAd production. (We also produced pdelta28-TNF-siRNA vector for knockdown of TNF-alpha.)
(5) We published the article for selective gene therapy for the neurons with tissue specific targeting HDAd system. And we made the presentation about them at severa meeting and propagated the usefulness and the possibilities in future of our studies.

Research Products

• [Journal Article] Hyperglycemia induces oxidative stress and impairs axonal transport rates in mice. (2010)
  • Author(s): Sharma R, Buras E, Terashima T, Serrano F, Massaad CA, Hu L, Bitner B, Inoue T, Chan L, Pautler RG.
  • Journal Title: PLoS One 5
  • Peer Reviewed
• [Journal Article] DRG-targeted helper-dependent adenoviruses mediate selective gene delivery for therapeutic rescue of sensory neuronopathies in mice. (2009)
  • Author(s): Terashima T, Oka K, Kritz AB, Kojima H, Baker AH, Chan L.
  • Journal Title: J Clin Invest 119 Pages: 2100-2112
  • Peer Reviewed
• [Journal Article] A neuronal VLDLR variant lacking the third complement-type repeat exhibits high capacity binding of apoE containing lipoproteins. (2009)
  • Author(s): Sakai K, Tiebel O, Ljungberg MC, Sullivan M, Lee HJ, Terashima T, Li R, Kobayashi K, Lu HC, Chan L, Oka K.
  • Journal Title: Brain Res 1276 Pages: 11-21
  • Peer Reviewed
• [Journal Article] DRG-targeted helper-dependent adenoviruses mediate selective gene delivery for therapeutic rescue of sensory neuronopathies in mice (2009)
  • Author(s): 寺島智也
  • Journal Title: Journal of Clinical Investigation 119 Pages: 2100-2112
  • Peer Reviewed
• [Presentation] Lawrence Chan DRG-targeted helper-dependent adenovirus vectorによる感覚神経選択的遺伝子治療 (2010)
  • Author(s): 寺島智也、Kazuhiro Oka、Angelika B.Kritz、小島秀人、山川勇、川合寛道、真田充、片山由理、Andrew H.Baker
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-21
• [Presentation] DRG-targeted helper-dependent adenovirus vectorによる感覚神経選択的遺伝子治療 (2010)
  • Author(s): 寺島智也
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2010-05-21
• [Presentation] Lawrence Chan. マウス後根神経節標的ヘルパー依存型アデノウイルスベクターによる感覚神経細胞障害の選択的遺伝子治療 (2010)
  • Author(s): 寺島智也、Kazuhiro Oka、Angelika B.Kritz、小島秀人、山川勇、川合寛道、真田充、片山由理、Andrew H.Baker
  • Organizer: 第9回日本再生医療学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-03-19
• [Presentation] マウス後根神経節標的ヘルパー依存型アデノウイルスベクターによる感覚神経細胞障害の選択的遺伝子治療 (2010)
  • Author(s): 寺島智也
  • Organizer: 第9回日本再生医療学会総会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2010-03-19
• [Presentation] Andrew H Baker and Lawrence Chan. ENGI NEERING DRG-TARGETED HELPER-DEPENDENT A DENOVIRUSES FOR SELECTIVE GENE DELIVERY (2010)
  • Author(s): Tomoya Terashima, Kazuhiro Oka, Angelika B Kritz, Hideto Kojima, Isamu Yamakawa, Hiromichi Kawai, Mitsuru Sanada
  • Organizer: 第16回日本遺伝子治療学会学術集会
  • Place of Presentation: 栃木
• [Presentation] ENGINEERING DRG-TARGETED HELPER-DEPENDENT ADENOVIRUSES FOR SELECTIVE GENE DELIVERY (2010)
  • Author(s): 寺島智也
  • Organizer: 第16回日本遺伝子治療学会学術集会
  • Place of Presentation: 栃木県総合文化センター(栃木県)
• [Presentation] Lawrence Chan. Engineering DRG-targeted helper-dependent adenoviruses for selective gene delivery. (2009)
  • Author(s): Tomoya Terashima, Kazuhiro Oka, Angelika B Kritz, Hideto Kojima, Andrew H Baker
  • Organizer: 第19回世界神経会議(World Congress of Neurology)
  • Place of Presentation: タイ王国
  • Year and Date: 2009-10-28
• [Presentation] Engineering DRG-targeted helper-dependent adenoviruses for selective gene delivery (2009)
  • Author(s): 寺島智也
  • Organizer: 第19回世界神経会議 (World Congress of Neurology)
  • Place of Presentation: タイ王国・バンコク
  • Year and Date: 2009-10-28
• [Remarks] 滋賀医科大学ホームページ
  • URL: http://www.shiga-med.ac.jp/education/newresearch/2009_terashima.html
• [Remarks] ベイラー医科大学ホームページ
  • URL: http://www.bcm.edu/news/item.cfm?newsID=1467