2019 Fiscal Year Final Research Report
CRISPR/Cas9 mediated identification of novel gene targets for XPA-associated skin cancer using in vitro reconstituted skin from iPS cells
| Project/Area Number |
17K07165
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ウォルツェン クヌート 京都大学, iPS細胞研究所, 准教授 (50589489)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | Human iPSCs / CRISPR/Cas9 / Squamous Cell Carcinoma / Skin differentiation / Xeroderma pigmentosum |
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| Outline of Final Research Achievements |
Skin cancer develops as a result of the accumulation of mutations in stem cells of the tissue. Exposure to ultraviolet light leads to accumulation of mutations in the skin; however, the understanding of how skin malignancy progresses is poor and imposes a bottleneck to designing efficient treatments to overcome the disease.
In order to identify novel oncogenes and tumor suppressor genes as targets of UV-induced mutagenesis, I took advantage of iPSCs and gene editing technologies. Xeroderma pigmentosum (XP) patient-derived iPSCs were obtained. The XPA mutation was repaired in order to generate isogenic control cells. Then, I engineered genetically the aforementioned cells to be able to delete tumor suppressor genes using CRISPR/Cas9 nuclease. Application of UV-induced mutagenesis in conjunction with CRISPR/Cas9 in iPSC differentiated skin keratinocytes may allow to induce cell transformation and identify cancer causative mutations using massive parallel sequencing.
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| Free Research Field |
Skin differentiation, gene editing
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| Academic Significance and Societal Importance of the Research Achievements |
The aim of this work is to generate a model of skin cancer in vitro. The model permits to emulate the acquisition of cancer driver mutations and may allow design custom-made individual patient therapies, compound screening and drug development thus reducing the use of animals for experimentation.
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