Homologous recombination-mediated gene correction in iPS cells o Ornithine transcarbamylase deficiency

• Project/Area Number: 23659511
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: TSUCHIYA Shigeru 東北大学, 大学院・医学系研究科, 名誉教授 (30124605)
• Co-Investigator(Kenkyū-buntansha): SAKAMOTO Osamu 東北大学, 大学病院, 講師 (20333809) ; UCHIYAMA Toru 東北大学, 大学病院, 助教 (10436107)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝子修復 / iPS 細胞 / OTC 欠損症 / iPS細胞 / OTC欠損症

Research Abstract

iPS cells was derived from fibroblasts of OTCD. While the cells were transduced with AAV targeting vector for the homologous recombination-mediated gene correction, corrected clones were not obtained. For making iPS cells, we developed the strategies of culturing keratinocytes from human hair. These cells can be passaged and cultured for a long time. The establishment of iPS cells using these cells is in progress.

Research Products

• [Journal Article] Effect of a blackout in pediatric patients with home medical devices during the 2011 eastern Japan earthquake (2013)
  • Author(s): Nakayama T, Tanaka S, Uematsu M, Kikuchi A, Hino-Fukuyo N, Morimoto T, Sakamoto O, Tsuchiya S, Kure S
  • Journal Title: Brain Dev Volume: (In press)
  • Peer Reviewed
• [Journal Article] Effect of a blackout in pediatric patients with home medical devices during the 2011 eastern Japan earthquake. (2013)
  • Author(s): Tojo Nakayama
  • Journal Title: Brain Dev. Volume: in press Issue: 2 Pages: 143-147
  • DOI: 10.1016/j.braindev.2013.02.001
  • Peer Reviewed
• [Journal Article] Development of a Multi-Step Leukemogenesis Model of MLL-Rearranged Leukemia Using Humanized Mice (2012)
  • Author(s): Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamuta K, Ishii N
  • Journal Title: PLos One Volume: 7(6)
  • Peer Reviewed
• [Journal Article] Foamy Virus Vector-mediated Gene Correction of a Mouse Model of Wiskott-Aldrich Syndrome (2012)
  • Author(s): Uchiyama T, Adriani M, Jagadeesh GJ, Paine A, Candotti F
  • Journal Title: Mol. Ther Volume: 20(6) Issue: 6 Pages: 1270-1279
  • DOI: 10.1038/mt.2011.282
  • Peer Reviewed
• [Journal Article] Casitas B-cell lymphoma mutation in childhood T -cell acute lymphoblastic leukemia (2012)
  • Author(s): Saito Y, Aoki Y, Muramatsu H, Makishima H, Maciejewski JP, Imaizumi M, Rikiishi T, Sasahara Y, Kure S, Niihori T, Tsuchiya S, Kojima S, Matsubara Y
  • Journal Title: Leuk Res Volume: 36(8) Issue: 8 Pages: 1009-15
  • DOI: 10.1016/j.leukres.2012.04.018
  • Peer Reviewed
• [Journal Article] Unusual ribbon-like periventricular heterotopia with congenital cataracts in a Japanese girl (2012)
  • Author(s): Tsuburaya R, Uematsu M, Kikuchi A, Hino-Fukuyo N, Kunishima S, Kato M, Haginoya K, Tsuchiya S
  • Journal Title: Am J Med Genet A Volume: 158A(3) Issue: 3 Pages: 674-7
  • DOI: 10.1002/ajmg.a.34258
  • Peer Reviewed
• [Journal Article] Successful cord blood transplantation with reduced-intensity conditioning for childhood cerebral X-linked adrenoleukodystrophy at advanced and early stages (2012)
  • Author(s): Niizuma H, Uematsu M, Sakamoto O, Uchiyama T, Horino S, Onuma M, Matsuhashi T, Rikiishi T, Sasahara Y, Minegishi M, Tsuchiya S.
  • Journal Title: Pediatr Transplant Volume: 16(2) Issue: 2
  • DOI: 10.1111/j.1399-3046.2011.01539.x
  • Peer Reviewed
• [Journal Article] Two novel mutations in the lactase gene in a Japanese infant with congenital lactase deficiency. (2012)
  • Author(s): Nao Uchida
  • Journal Title: Tohoku J Exp Med. Volume: 227 Pages: 69-72
  • Peer Reviewed
• [Journal Article] Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice (2012)
  • Author(s): Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamura K, and Ishii N.
  • Journal Title: PLoS ONE Volume: 7(6) Issue: 6 Pages: e37892-e37892
  • DOI: 10.1371/journal.pone.0037892
  • Peer Reviewed
• [Journal Article] Nationwide Survey of Patients with Primary Immunodeficiency Diseases in Japan (2011)
  • Author(s): Ishimura M, 他
  • Journal Title: Journal of clinical immunology Volume: (in press) Issue: 6 Pages: 968-976
  • DOI: 10.1007/s10875-011-9594-7
  • Peer Reviewed
• [Journal Article] Octa-arginine mediated delivery of wild-type Lnk protein inhibits TPO-induced M-MOK megakaryoblastic leukemic cell growth by promoting apoptosis (2011)
  • Author(s): Looi CY, Imanishi M, Takaki S, Sato M, Chiba N, Sasahara Y, Futaki S, Tsuchiya S, Kumaki S
  • Journal Title: PLos One Volume: 6(8)
  • Peer Reviewed
• [Journal Article] Defective inhibition of B-cell proliferation by Wiskott-Aldrich syndrome protein-deficient regulatory T cells (2011)
  • Author(s): Adriani M, Jones KA, Uchiyama T, Kirby MR, Silvin C, Anderson SM, Candotti F
  • Journal Title: Blood Volume: 117(24) Issue: 24 Pages: 6608-6611
  • DOI: 10.1182/blood-2010-12-322834
  • Peer Reviewed
• [Journal Article] Quality assessment of umbilical cord blood units at the time of transplantation (2011)
  • Author(s): Kudo Y, Minegishi M, Seki O, Takahashi H, Suzuki A, Narita A, Sato Y, Abe M, Ishioka N, Harigae H, Tsuchiya S
  • Journal Title: Int J Hematol Volume: 93(5) Pages: 645-651
  • NAID: 10029535180
  • Peer Reviewed
• [Journal Article] Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells (2011)
  • Author(s): Saito M,…, Takada H, et al
  • Journal Title: J Exp Med Volume: 208 Issue: 2 Pages: 235-249
  • DOI: 10.1084/jem.20100799
  • Peer Reviewed
• [Journal Article] A female case of West syndrome with remission of spams following multiple cerebral hemorrhages (2011)
  • Author(s): Hino-Fukuyo N, Haginoya K, Uematsu M, Tsuchiya S
  • Journal Title: Brain Dev Volume: 33(8) Issue: 8 Pages: 678-682
  • DOI: 10.1016/j.braindev.2010.10.010
  • Peer Reviewed
• [Presentation] リツキシマブが有効であった乳児自己免疫性溶血性貧血の1例 (2012)
  • Author(s): 森谷邦彦、松橋徹朗、小沼正栄、内山徹、力石健、浅田洋司、鈴木潤、笹原洋二、呉繁夫
  • Organizer: 第54回小児血液・がん学会
  • Place of Presentation: 横浜
  • Year and Date: 2012-11-30
• [Presentation] Fabio Candotti Development of Foamy Virus Vector System for Primaryimmunodeficiencies (2012)
  • Author(s): Toru Uchiyama、Satoshi Horino、Yoji Sasahara、Naoto Ishii
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
  • Year and Date: 2012-06-28
• [Presentation] Spontaneous reversionを伴う原発性免疫不全症2症例における長期的臨床経過の検討 (2012)
  • Author(s): 笹原洋二、佐藤美季、斉藤由佳、小沼正栄、入江正寛、内山徹、力石健、呉繁夫
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-04-20
• [Presentation] 骨髄非破壊的前処置にて同種骨髄移植を施行した慢性活動性EBV感染症4例の臨床的検討 (2012)
  • Author(s): 笹原洋二、渡辺祐子、小沼正栄、新妻秀剛、内山徹、力石健、峯岸政好、久間木悟、土屋滋
  • Organizer: 第34回日本造血幹細胞移植学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-02-24
• [Presentation] RISTを施行した当科年長児および成人期WAS/XLT3症例の臨床的検討 (2012)
  • Author(s): 笹原洋二、力石健、北沢博、内山徹、森尾友宏、峯岸政好、久間木悟、土屋滋
  • Organizer: 第5回日本免疫不全症研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-01-21
• [Presentation] Functional roles of WIP in Wiskott-Aldrich Syndrome (2012)
  • Author(s): Yoji Sasahara
  • Organizer: 8th Society of Asian Pediatric Research
  • Place of Presentation: Korea,Seoul
• [Presentation] Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice. (2012)
  • Author(s): 森谷邦彦
  • Organizer: 第54回小児血液がん学会
  • Place of Presentation: 横浜
• [Presentation] X連鎖重症複合免疫不全症に対する骨髄非破壊的前処置を用いた非血縁者間臍帯血移植B細胞機能 (2012)
  • Author(s): 久間木悟
  • Organizer: 第54回小児血液がん学会
  • Place of Presentation: 横浜
• [Presentation] SKY法が複雑型染色体異常の同定に有用であった急性白血病の2例 (2011)
  • Author(s): 片山紗乙莉、小沼正栄、内山徹、新妻秀剛、力石健、笹原洋二、呉繁夫
  • Organizer: 第53回日本小児血液・がん学会学術集会
  • Place of Presentation: 前橋
  • Year and Date: 2011-11-25
• [Presentation] フォーミーウイルスベクターによるWiskott-Aldrich症候群への遺伝子治療 (2011)
  • Author(s): 内山徹、Fabio Candotti、土屋滋
  • Organizer: 第114回日本小児科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-08-12
• [Presentation] The progress of stem cell gene therapy for primary immunodeficiency (2011)
  • Author(s): Toru Uchiyama
  • Organizer: 第17回日本遺伝子治療学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-15