Generation of gene therapy method for ataxia-telangiectasia using a human artificial chromosome

• Project/Area Number: 19790246
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Human genetics
• Research Institution: Tottori University
• Principal Investigator: KAZUKI Yasuhiro Tottori University, 大学院・医学系研究科, 助教 (90403401)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥540,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: ヒト人工染色体 / 遺伝子治療 / 染色体工学 / 毛細血管拡張性運動失調症 / ES細胞 / 再生医療 / 遣伝子治療

Research Abstract

To generate gene therapy vector for ataxia telangiectasia (AT), we constructed novel human artificial chromosome (HAC) containing ATM gene, which is mutated in ataxia telangiectasia (AT) patients. The ATM-HAC were transferred into ATM-deficient cell line derived from a AT patient. The ATM-deficient phenotypes of gene regulation and radiation sensitivity were complemented by introducing the ATM-HAC. Furthermore, the ATM-HAC was stably maintained in the cell lines. Thus, the ATM-HAC vector will be useful for gene therapy of AT.

Research Products

• [Journal Article] Complete genetic correction of iPS cells from Duchenne muscular dystrophy. (2010)
  • Author(s): Kazuki Y., Hiratsuka M., Takiguchi M., Osaki M., Kajitani N., Hoshiya H., Hiramatsu K., Yoshino T., Kazuki K., Ishihara C., Takehara S., Higaki K., Nakagawa M., Takahashi K., Yamanaka S., Oshimura M.
  • Journal Title: Mol. Therapy. Volume18,number2 Pages: 386-93
  • Peer Reviewed
• [Journal Article] 幹細胞のゲノム操作:ヒト人工染色体ベクターの開発 (2009)
  • Author(s): 香月康宏, 押村光雄
  • Journal Title: ゲノム医学 Vol.9,No.3 Pages: 37-40
• [Journal Article] A highly stable and non-integrated human artificial chromosome (HAC) containing the 2. 4Mb entire human dystrophin gene. (2009)
  • Author(s): Hoshiya H., Kazuki Y., Abe S., Takiguchi M., Kajitani N., Watanabe Y., Yoshino T., Shirayoshi Y., Higaki K., Messina G., Cossu G., Oshimura M.
  • Journal Title: Mol. Therapy. Volume17,number2 Pages: 309-17
  • Peer Reviewed
• [Journal Article] Enhanced apoptosis during early neuronal differentiation in mouse ES cells with autosomal imbalance. (2009)
  • Author(s): Kai Y., Wang CC., Kishigami S., Kazuki Y., Abe S., Takiguchi M., Shirayoshi Y., Inoue T., Ito H., Wakayama T., Oshimura M.
  • Journal Title: Cell Res. Volume19,number2 Pages: 247-58
  • Peer Reviewed
• [Journal Article] Complete genetic correction of iPS cells from Duchenne muscular dystrophy (2009)
  • Author(s): Kazuki Y.
  • Journal Title: Mol.Therapy 18 Pages: 386-393
  • Peer Reviewed
• [Journal Article] ヒト人工染色体ベクターの開発 (2009)
  • Author(s): 香月康宏
  • Journal Title: ゲノム医学 9 Pages: 37-40
• [Journal Article] A highly stable and non-integrated human artificial chromosome(HAC) containing the 2.4Mb entire human dystrophin gene (2009)
  • Author(s): Hoshiya H.
  • Journal Title: Mol. Therapy 17 Pages: 309-317
  • Peer Reviewed
• [Journal Article] Enhanced apoptosis during early neuronal differentiation in mouse ES cells with autosomal imbalance (2009)
  • Author(s): Kai Y.
  • Journal Title: Cell Res 19 Pages: 247-258
  • Peer Reviewed
• [Journal Article] Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector. (2008)
  • Author(s): Shitara S, Kakeda M, Nagata K, Hiratsuka M, Sano A, Osawa K, Okazaki A, Katoh M, Kazuki Y, Oshimura M, Tomizuka K.
  • Journal Title: Biochem Biophys Res Commun. Volume369,number3 Pages: 807-11
  • Peer Reviewed
• [Journal Article] Correction of a genetic defect in multipotent germline stem cells using a human artificial chromosome. (2008)
  • Author(s): Kazuki Y, Hoshiy H, Kai Y, Abe S, Takiguch M, Osaki M, Kawazoe S, Katoh M, Kanatsu-Shinohara M, Inoue K, Kajitani N, Yoshino T, Shirayoshi S, Ogura A, Shinohara T, Barrett JC, Oshimura M.
  • Journal Title: Gene therapy Volume15,number8 Pages: 617-24
  • Peer Reviewed
• [Journal Article] Telomerase-mediated life-span extension of primary fibroblasts by human artificial chromosome (HAC) vector. (2008)
  • Author(s): Shitara S
  • Journal Title: Biochem Biophys Res Commun. 369 Pages: 807-811
  • Peer Reviewed
• [Journal Article] Correction of a genetic defect in multipotent germline stem cell using a human artificial chromosome. (2008)
  • Author(s): Kazuki Y
  • Journal Title: Gene Ther. 15 Pages: 617-624
  • Peer Reviewed
• [Presentation] 染色体工学技術を用いたヒト型モデル動物の作製と応用 (2009)
  • Author(s): 香月康宏
  • Organizer: 第129回日本薬学会年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-26
• [Presentation] ヒト型P450薬物代謝酵素発現マウス (2009)
  • Author(s): 香月康宏, 小林カオル, 千葉寛, 押村光雄
  • Organizer: 第56回日本実験動物学会総会
  • Place of Presentation: 埼玉
• [Presentation] 染色体工学技術を用いたヒト型モデル動物の作製と応用 (2009)
  • Author(s): 香月康宏, 押村光雄
  • Organizer: 第129回日本薬物学会年会
  • Place of Presentation: 京都
• [Presentation] A novel human artificial chromosome (HAC) for gene therapy and animal transgenesisASGT 11^<th> annual meeting (2008)
  • Author(s): Kazuki Y
  • Organizer: ASGT 11^<th> annual meeting
  • Place of Presentation: USA, Boston
  • Year and Date: 2008-05-30
• [Presentation] A novel human artificial chromosome (HAC) for gene therapy and animal transgenesis (2008)
  • Author(s): Kazuki Y., Hoshiya H., Abe S., Takiguchi M., Iida Y., Watanabe Y., Osaki M., Katoh M., Kajitani N., Yoshino T., Shirayoshi Y., Hiratsuka M., Kurimasa K., Oshimura M.
  • Organizer: ASGT 11th annual meeting
  • Place of Presentation: U.S.A.
• [Presentation] 遺伝子治療に向けた新規遺伝子治療用ヒト人工染色体ベクターの開発 (2008)
  • Author(s): 香月康宏, 星谷英寿, 甲斐義輝, 阿部智志, 滝口正人, 飯田雄一, 渡辺義徳, 尾崎克彦, 梶谷尚世, 吉野とう子, 白吉安昭, 富松望, 平塚正治, 栗政明弘, 押村光雄
  • Organizer: 第7回日本再生医療学会総会
  • Place of Presentation: 名古屋
• [Presentation] Genetic restoration of ataxia telangiectasia cells using a human artificial chromosome mediated- genomic cloning system (2007)
  • Author(s): Kazuki Y
  • Organizer: ASGT 10th annual meeting
  • Place of Presentation: USA,Seattle
  • Year and Date: 2007-06-01
• [Presentation] Genetic restoration of ataxia telangiectasia cells using a human artificial chromosome mediatedgenomic cloning system (2007)
  • Author(s): Kazuki Y., Hoshiya, H., Kai Y., Abe S., Takiguchi M., Osaki M., Yuichi I., Mizutani E., Kajitani N., Yoshino T., Shirayoshi Y., Tomimatsu N., Hratsuka M., Kurimasa A., Wakayama T., Oshimura, M.
  • Organizer: ASGT 10th annual meeting
  • Place of Presentation: U.S.A.
• [Patent(Industrial Property Rights)] ヒト人工染色体(HAC)ベクター及びヒト人工染色体(HAC)を有するヒト細胞医薬 (2007)
  • Inventor(s): 掛田実, 富塚一磨, 押村光雄, 香月康宏
  • Industrial Property Rights Holder: キリンファーマ株式会社
  • Filing Date: 2007-07-06
• [Patent(Industrial Property Rights)] ヒト人工染色体(HAC)ベクター及びヒト人工染色体(HAC)を有するヒト細胞医薬 (2007)
  • Inventor(s): 掛田実、富塚一磨、押村光雄、香月康宏
  • Industrial Property Rights Holder: キリンファーマ株式会社
  • Filing Date: 2007-07-06
  • Overseas