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

2012 Fiscal Year Final Research Report

• 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
• Keywords: 遺伝子修復 / 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] 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) Pages: e37892
  • DOI: doi:10.137/journal.pone. 0037892
  • 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) Pages: 1270-1279
  • DOI: 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, Maciejewski JP, Imaizumi M, Rikiishi T, Sasahara Y, Kure S, Niihori T, Tsuchiya S, Kojima S, Maysubara Y
  • Journal Title: Leuk Res Volume: 36(8) Pages: 1009-1015
  • DOI: 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 Volume: 158A(3) Pages: 674-677
  • DOI: doi:10.1002/ajmg.a.34258
  • Peer Reviewed
• [Journal Article] Nationwide survey of patients with primary immunodeficiency disease in Japan (2011)
  • Author(s): Ishimura M, Takada H, Imai k, Sasahara Y, Kanegane H, Nishinomori R, Morio T, Heike T, Kobayashi M, Ariga T, Tsuchiya S, Nonoyama S, Miyawaki T, Hara T
  • Journal Title: J Clin Immunol Volume: 31(6) Pages: 968-976
  • DOI: 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) Pages: e23640
  • DOI: doi:10.137/journal.pone.0023640
  • 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) Pages: 6608-6611
  • DOI: 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
  • DOI: doi:10.1007/s.12185-011-0830-y
  • 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, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Nonoyama S, Karasuyama H, Minegishi Y
  • Journal Title: J Exp Med Volume: 208(2) Pages: 235-249
  • DOI: 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) Pages: 678-682
  • DOI: doi:10.1016/j.braindev.2010.10.010
  • Peer Reviewed
• [Journal Article] Successful cord blood transplantation with reduced-intensity conditioning for childhood cerebral X-linked adrenoleukodystorophy at advanced and early stages. Pediatr
  • 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: Transplant Volume: 16(2) Pages: E63-70
  • DOI: doi:10.1111/j.1399-3046.2011.01539.x
  • 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] 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