2022 Fiscal Year Final Research Report
Development of expression analysis for retinitis pigmentosa causative genes using peripheral blood by epigenome editing
| Project/Area Number |
20K09765
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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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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中澤 徹 東北大学, 医学系研究科, 教授 (30361075)
藤田 幸輔 名古屋大学, 医学系研究科, 助教 (80708115)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 網膜色素変性 / ゲノム編集 / リンパ球 |
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| Outline of Final Research Achievements |
The genetic basis of Japanese retinitis pigmentosa remains largely unknown. Therefore, using genome editing technology, we developed a technique for over expression of a specific retinitis pigmentosa-causing gene promoter by unmethylating it in lymphoblasts derived from patients with retinitis pigmentosa. First, the EYS gene, which has the highest frequency as a pathogenic gene in Japanese patients with retinitis pigmentosa, was targeted for development. We performed mRNA analysis of the EYS gene expressed by genome editing in a patient-derived lymphoblastoid cell lines, and confirmed that the disease-causing mutation could be identified by comparing it with the patient's genomic information. It is possible to develop a comparatively simple and inexpensive genetic test method.
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| Free Research Field |
眼科学
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| Academic Significance and Societal Importance of the Research Achievements |
本邦の失明原因の上位である網膜色素変性は難治性の遺伝性疾患であるが、大半の患者で病因変異が特定できていない。mRNA解析が有効な補助診断となりえるが、血液など容易に採取可能な患者由来サンプルで有用な結果を得るのは困難であった。この状況において、本研究では、患者リンパ球由来の網膜特異的遺伝子の強制発現細胞株を樹立し、遺伝子解析に対する有効性を示すことができた。この技術が発展すれば遺伝子診断の補助検査として広く普及する可能性がある。さらに、本技術は、網膜疾患以外の遺伝性疾患や非遺伝性疾患の病態解明や治療開発にも応用可能であり、汎用性と波及効果が極めて高く、その意義は大きい。
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