Development of a gene therapy for congenital phagocyte disorder using both genome editing and iPS cell technology
| Project/Area Number |
15H04874
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shinshu University |
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Principal Investigator |
Koike Kenichi 信州大学, 医学部, 特任教授 (40143979)
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| Co-Investigator(Kenkyū-buntansha) |
中沢 洋三 信州大学, 医学部, 教授 (60397312)
重村 倫成 信州大学, 学術研究院医学系(医学部附属病院), 講師 (70623916)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | iPS細胞 / ゲノム修飾 / 先天性好中球減少症 / 遺伝子治療 / 再生医学 / 白血病発症 / 先天性食細胞異常症 |
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| Outline of Final Research Achievements |
In parallel with genetic editing experiments of iPS cells established from a patient with ELANE-mutated severe congenital neutropenia, we performed genetic editing experiments on iPS cells derived from a patient with juvenile myelomonocytic leukemia (JMML). Both iPS cells with PTPN11 gene mutation and those with wild type of PTPN11gene were established from a JMML patient. Mutant iPS cells possessed significantly higher ability to generate CD34 positive cells. In addition, whole-exome sequencing and Sanger sequencing revealed that JMML iPSCs with PTPN11 mutation possessed OSBP2 mutation, while JMML iPSCs with no PTPN11 mutation did not carry OSBP2 mutation. By homologous recombination using zinc finger nuclease, we corrected PTPN11 mutation in iPSCs with both PTPN11 mutation and OSBP2 mutation, and transduced PTPN11 mutation into JMML iPSCs with wild type of the two genes. The results suggest that PTPN11 mutation itself contributes to leukemogenesis of this patient.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Dramatic Reduction in Tumor Size During 5 Months of Pazopanib Therapy in Combination With Ifosfamide, Carboplatin, and Etoposide in an Early Infant With Progressive Soft Tissue Sarcoma.2017
Author(s)
Watanabe T, Kurata T, Sano K, Suzuki S, Kaneko T, Motobayashi M, Shigemura T, Sumi T, Koike K, Nakazawa Y
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Journal Title
J Pediatr Hematol Oncol
Volume: 39
Pages: 154-6
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes.2017
Author(s)
Muramatsu H, Okuno Y, Yoshida K, Shiraishi Y, Doisaki S, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Takahashi Y, Kanno H, Yamaguchi H, Ohga S, Manabe A, Harigae H, Kunishima S, Ishii E, Kobayashi M, Koike K, Watanabe K, Ito E, Takata M, Yabe M, Ogawa S, Miyano S, Kojima S.
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Journal Title
Genetics in Medicine
Volume: -
Pages: 796-802
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Pazopanib Therapy in Combination With Ifosfamide, Carboplatin, and Etoposide in an Early Infant With Progressive Soft Tissue Sarcoma.2017
Author(s)
Watanabe T, Kurata T, Sano K, Suzuki S, Kaneko T, Motobayashi M, Shigemura T, Sumi T, Koike K, Nakazawa Y.
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Journal Title
J Pediatr Hematol Oncol
Volume: 39
Pages: 154-156
Related Report
Peer Reviewed / Open Access
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[Journal Article] Viral load and ganciclovir (GCV) concentration in cerebrospinal fluid of patients successfully treated with GCV or valGCV for human herpesvirus 6 encephalitis/myelitis following umbilical cord blood transplantation.2016
Author(s)
D. Morita, K. Hirabayashi, Y. Katsuyama, H. Morokawa, M. Motobayashi, T. Kurata, T. Shigemura, M. Tanaka, Y. Inaba, K. Koike, Y. Nakazawa.
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Journal Title
Transpl Infect Dis
Volume: 18
Pages: 773-776
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction.2016
Author(s)
Hirabayashi K, Kurata T, Horiuchi K, Saito S, Shigemura T, Tanaka M, Yanagisawa R, Matsuda K, Sakashita K, Koike K, Nakazawa Y
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Journal Title
Pediatric Blood & Cancer
Volume: 63
Pages: 709-11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Analysis of KRAS and NRAS gene mutations in Arab Asian children with acute leukemia: High frequency of RAS mutations in acute lymphoblastic leukemia.2015
Author(s)
Al-Kzayer LF, Sakashita K, Al-Jadiry MF, Al-Hadad SA, Ghali HH, Uyen LT, Liu T, Matsuda K, Abdulkadhim JM, Al-Shujairi TA, Matti ZI, Sughayer MA, Rihani R, Madanat FF, Inoshita T, Kamata M, Koike K.
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Journal Title
Pediatr Blood Cancer
Volume: 62
Pages: 2157-61
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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