Development of disease-modeling technology using hierarchical genome/epigenome editing
Project/Area Number |
16K18478
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
System genome science
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Research Institution | Hiroshima University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | がん / ゲノム編集 / エピゲノム編集 / マイクロホモロジー媒介性末端結合 / MMEJ / ゲノム生物工学 / CRISPR-Cas9 / TALEN |
Outline of Final Research Achievements |
In this research, we developed the genome/epigenome editing technologies enabling disease modeling caused by genomic and/or epigenomic abnormality that multiplexly occurs in a single cell. Regarding genome editing, we achieved the improvement of MMEJ-dependent gene knock-in (PITCh) and the development of automated design tool of PITCh knock-in. In addition, we realized simultaneous gene knock-in into multiple gene loci using the improved PITCh system. Regarding epigenome editing, we constructed the TREE system for hyper accumulation of effector molecules, showing superior editing effect compared to the conventional systems. Collectively, the technology capable of modeling complex multifactorial pathogenesis was established in terms of both genome and epigenome editing.
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Report
(3 results)
Research Products
(57 results)
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[Journal Article] Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.2018
Author(s)
Shukunami C, Takimoto A, Nishizaki Y, Yoshimoto Y, Tanaka S, Miura S, Watanabe H, Sakuma T, Yamamoto T, Kondoh G, Hiraki Y.
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Journal Title
Scientific reports
Volume: 8
Issue: 1
Pages: 1-12
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair.2017
Author(s)
Tsuda M, Cho K, Ooka M, Shimizu N, Watanabe R, Yasui A, Nakazawa Y, Ogi T, Harada H, Agama K, Nakamura J, Asada R, Fujiike H, Sakuma T, Yamamoto T, Murai J, Hiraoka M, Koike K, Pommier Y, Takeda S, Hirota K.
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Journal Title
PLos One
Volume: 12
Issue: 11
Pages: e0188320-e0188320
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology2017
Author(s)
Abe S, Kobayashi K, Oji A, Sakuma T, Kazuki K, Takehara S, Nakamura K, Okada A, Tsukazaki Y, Senda N, Honma K, Yamamoto T, Ikawa M, Chiba K, Oshimura M, Kazuki Y.
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Journal Title
Sci Rep
Volume: 7
Issue: 1
Pages: 15189-15189
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detailed analysis of targeted gene mutations caused by the Platinum-Fungal TALENs in Aspergillus oryzae RIB40 strain and a ligD disruptant2017
Author(s)
Mizutani, O., Arazoe, T., Toshida, K., Hayashi, R., Ohsato, S., Skuma, T., Yamamoto, T., Kuwata, S. and Yamada, O.
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Journal Title
Journal of Biotechnology and Bioengineering
Volume: 3
Issue: 3
Pages: 287-293
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Establishment of expanded and streamlined pipeline of PITCh knock-in - a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO2017
Author(s)
Nakamae K, Nishimura Y, Takenaga M, Nakade S, Sakamoto N, Ide H, Sakuma T, Yamamoto T
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Journal Title
Bioengineered
Volume: -
Issue: 3
Pages: 302-308
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Systematic cellular disease models reveal synergistic interactions of trisomy 21 and GATA1 mutations in hematopoietic abnormalities2016
Author(s)
K. Banno, S. Omori, K. Hirata, N. Nawa, N. Nakagawa, K. Nishimura, M. Ohtaka, M. Nakanishi, T. Sakuma, T. Yamamoto, T. Toki, E. Ito, T. Yamamoto, C. Kokubu, J. Takeda, H. Taniguchi, H. Arahori, K. Wada, Y. Kitabatake and K. Ozono
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Journal Title
Cell Reports
Volume: 15
Issue: 6
Pages: 1-15
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functional consequence of fibulin-4 missense mutations associated with vascular and skeletal abnormalities and cutis laxa2016
Author(s)
Sasaki T, Hanisch FG, Deutzmann R, Sakai LY, Sakuma T, Miyamoto T, Yamamoto T, Hannappel E, Chu ML, Lanig H, von der Mark K
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Journal Title
Matrix Biol
Volume: 56
Pages: 132-149
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing.2016
Author(s)
Sato K, Oiwa R, Kumita W, Henry R, Sakuma T, Ito R, Nozu R, Inoue T, Katano I, Sato K, Okahara N, Okahara J, Shimizu Y, Yamamoto M, Hanazawa K, Kawakami T, Kametani Y, Suzuki R, Takahashi T, Weinstein EJ, Yamamoto T, Sakakibara Y, Habu S, Hata J, Okano H, Sasaki E.
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Journal Title
Cell Stem Cell
Volume: 19
Issue: 1
Pages: 127-138
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Non-RVD mutations that enhance the dynamics of the TAL repeat array along the superhelical axis improve TALEN genome editing efficacy2016
Author(s)
Tochio,N., Umehara,K., Uewaki,J., Flechsig,H., Kondo,M., Dewa,T., Sakuma,T., Yamamoto,T., Saito,T., Togashi,T., Tate,S.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 37887-37887
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection2016
Author(s)
Toyonaga K, Torigoe S, Motomura Y, Kamichi T, Hayashi JM, Morita YS, Noguchi N, Chuma Y, Kiyohara H, Matsuo K, Tanaka H, Nakagawa Y, Sakuma T, Ohmuraya M, Yamamoto T, Umemura M, Matsuzaki G, Yoshikai Y, Yano I, Miyamoto T, Yamasaki S.
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Journal Title
Immunity
Volume: 45
Issue: 6
Pages: 1245-1257
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.2016
Author(s)
Aida T, Nakade S, Sakuma T, Izu Y, Oishi A, Mochida K, Ishikubo H, Usami T, Aizawa H, Yamamoto T, Tanaka K.
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Journal Title
BMC Genomics
Volume: 17
Issue: 1
Pages: 979-979
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Transcriptional regulation of a horizontally transferred gene from bacterium to chordate.2016
Author(s)
Sasakura Y, Ogura Y, Treen N, Yokomori R, Park SJ, Nakai K, Saiga H, Sakuma T, Yamamoto T, Fujiwara S, Yoshida K.
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Journal Title
Proc Biol Sci.
Volume: 283
Issue: 1845
Pages: 20161712-20161712
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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