2020 Fiscal Year Final Research Report
Construction of Cynomologus Monkey Model for Hereditary Retinal Diseases : Diseases Mechanisms and Therapeutic
| Project/Area Number |
17H06276
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| Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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| Allocation Type | Single-year Grants |
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| Research Field |
Surgery related to the biological and sensory functions and related fields
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| Research Institution | 独立行政法人国立病院機構(東京医療センター臨床研究センター) |
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Principal Investigator |
Iwata Takeshi 独立行政法人国立病院機構(東京医療センター臨床研究センター), 分子細胞生物学研究部, 部長 (90374157)
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| Co-Investigator(Kenkyū-buntansha) |
溝田 淳 帝京大学, 医学部, 教授 (10239262)
下澤 律浩 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 霊長類医科学研究センター, 主任研究員 (50300786)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Keywords | 医歯薬学 / 外科系臨床医学 / 眼科学 / 生化学・分子生物学 / ドルーゼン |
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| Outline of Final Research Achievements |
The human eye has unique structure only common to higher primates. Many of the inherited retinal diseases such as macular dystrophy and inherited glaucoma are difficult to replicate in mouse eye. Recent gene editing technology has revolutionized the development of knock-in or knock-out disease mice. However, gene edited non-human primate for inherited eye diseases has not been successful. In this project, we used Platinum TALEN technology developed by Dr. Yamamoto and Dr. Sakuma at Hiroshima University to develop autosomal recessive retinal diseases including retinitis pigmentosa, macular dystrophy, Leber congenital amaurosis, and inherited glaucoma. We have successfully designed the vector and injected and tested with fertilized egg from cynomolgus macaque monkey. Approximately, 80% of egg were gene edited, which shows significant increase of efficiency over CRISPR/Cas9, which we previously tried for over 5 years. We now have pregnant macaque for 2021 delivery.
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| Free Research Field |
分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によってカニクイザルの遺伝子改変技術が確立されれば、霊長類を利用した世界的な標準技術として定着する可能性が高い。遺伝子改変カニクイザルの作製によって貴重な実験材料の供給源になり、薬剤治療、遺伝子治療、再生医療、人工網膜などの治療開発に広く利用されることが期待される。カニクイザルは世界的に実験動物として利用されているアカゲザルと同様にマカカ属に分類される旧世界の霊長類であり、そのゲノム配列の相同性もきわめて高い。
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