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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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2017: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
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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 / 眼生化学・分子生物学 |
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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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| 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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Report
(3 results)
Research Products
(58 results)
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[Journal Article] Novel biallelic loss-of-function KCNV2 variants in cone dystrophy with supernormal rod responses.2019
Author(s)
Kutsuma T, Katagiri S, Hayashi T, Yoshitake K, Iejima D, Gekka T, Kohzaki K, Mizobuchi K, Baba Y, Terauchi R, Matsuura T, Ueno S, Iwata T, Nakano T.
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Journal Title
Documenta Ophthalmologica
Volume: 138(3)
Pages: 229-239
DOI
Related Report
Peer Reviewed
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[Journal Article] High-Resolution Retinal Imaging Reveals Preserved Cone Photoreceptor Density and Choroidal Thickness in Female Carriers of Choroideremia.2019
Author(s)
Suzuki K, Gocho K, Akeo K, Kikuchi S, Kubota D, Katagiri S, Fujinami K, Tsunoda K, Iwata T, Yamaki K, Igarashi T, Nakano T, Takahashi H, Hayashi T, Kameya S.
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Journal Title
Ophthalmic Surgery, Lasers and Imaging Retina
Volume: 50(2)
Pages: 76-85
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Compound heterozygous splice site variants in the SCLT1 gene highlight an additional candidate locus for Senior-Loken syndrome.2018
Author(s)
Katagiri S, Hayashi T, Yoshitake K, Murai N, Matsui Z, Kubo H, Satoh H, Matsufuji S, Takamura T, Yokoo T, Omori Y, Furukawa T, Iwata T, Nakano T.
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Journal Title
Sci Rep.
Volume: 8
Pages: 16733-16733
Related Report
Peer Reviewed
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[Journal Article] Effect of Timolol on Optineurin Aggregation in Transformed Induced Pluripotent Stem Cells Derived From Patient With Familial Glaucoma.2018
Author(s)
Inagaki S, Kawase K, Funato M, Seki J, Kawase C, Ohuchi K, Kameyama T, Ando S, Sato A, Morozumi W, Nakamura S, Shimazawa M, Iejima D, Iwata T, Yamamoto T, Kaneko H, Hara H.
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Journal Title
Investigative Ophthalmology & Visual Science
Volume: 59(6)
Pages: 2293-2304
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genome-wide association study identifies seven novel susceptibility loei for primary open-angle glaucoma2018
Author(s)
Shiga Y, Akiyama M, Nishiguchi K M, Sato K, Shimozawa N, Takahashi A, Momozawa Y, Hirata M, Matsuda K, Yamaji T, Iwasaki M, Tsugane S, Oze I, Mikami H, Naito M, Wakai K, Yoshikawa M, Miyake M, Yanaka T, et al.
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Journal Title
Human Molecular Genetics
Volume: 27
Issue: 8
Pages: 1486-1496
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy.2018
Author(s)
Khan KN, Kasilian M, Mahroo OAR, Tanna P, Kalitzeos A, Robson AG, Tsunoda K, Iwata T, Moore AT, Fujinami K, Michaelides M.
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Journal Title
Ophthalmology
Volume: 125(5)
Pages: 735-746
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genetic Variant Near PLXDC2 Influences the Risk of Primary Open-angle Glaucoma by Increasing Intraocular Pressure in the Japanese Population.2017
Author(s)
Mabuchi F, Mabuchi N, Takamoto M, Sakurada Y, Yoneyama S, Kashiwagi K, Iijima H, Yamagata Z, Aihara M, Iwata T, Araie M. Japan Glaucoma Society Omics Group (JGS-OG).
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Journal Title
Journal of Glaucoma
Volume: 26(11)
Pages: 963-966
DOI
Related Report
Peer Reviewed
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[Journal Article] A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration.2017
Author(s)
Yamashiro K, Mori K, Honda S, Kano M, Yanagi Y, Obana A, Sakurada Y, Sato T, Nagai Y, Hikichi T, Kataoka Y, Hara C, Koyama Y, Koizumi H, Yoshikawa M, Miyake M, Nakata I, Tsuchihashi T, Horie-Inoue K, et al.
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Journal Title
Scientific Reports
Volume: 7(1)
Pages: 9196-9196
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma.2017
Author(s)
Mabuchi F, Mabuchi N, Sakurada Y, Yoneyama S, Kashiwagi K, Iijima H, Yamagata Z, Takamoto M, Aihara M, Iwata T, Kawase K, Shiga Y, Nishiguchi KM, Nakazawa T, Ozaki M, Araie M; Japan Glaucoma Society Omics Group (JGS-OG).
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access
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