Development of the New Generation Humanize Bio-Cornea (I)-3

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Project title

Code/計畫編號

MOST104-2622-B001-003-CC1

Translated Name/計畫中文名

新世代擬人化生物人工角膜開發( I )-3

Project Coordinator/計畫主持人

Hong-Yi Gong

Funding Organization/主管機關

National Science and Technology Council

Co-Investigator(s)/共同執行人

吳金洌
耿全福

Department/Unit

Institute of Cellular and Organismic Biology, Academia Sinica

Website

https://www.grb.gov.tw/search/planDetail?id=11485461

Year

2015

Start date/計畫起

01-06-2015

Expected Completion/計畫迄

31-05-2016

Bugetid/研究經費

2500千元

ResearchField/研究領域

醫學工程

目前全球角膜性失明人口約有 1000 萬人，且每年以60 萬人的速度增加中，但現今一年僅有約 10 萬個眼角膜可供移植，眼角膜嚴重缺乏。然而異體角膜移植仍有免疫排斥、手術成功率低及角膜品質難以保障等問題，所以全球眼科研發團隊紛紛投入人工角膜開發，然而目前市面上可販售之商品選擇極少，使用材質與功效評估皆無法盡善盡美，甚至因此產生許多嚴重副作用，造成患者二次傷害。歐盟一項發表於Science Translational Medicine 的研究指出，利用基因轉殖合成人類膠原蛋白製備之生物合成眼角膜，期待能為等待角膜捐贈病患提供有效替代方案。本計畫合作廠商柏登生醫公司已開發出第一代以吳郭魚鱗片做為人工生物眼角膜之技術，在實驗動物中已經證實可行，但魚鱗中主要的魚類膠原蛋白質，在未來進入人體移植時，可能會產生人體排斥的問題，因此以基因轉殖技術將人類膠原蛋白基因轉入吳郭魚鱗片表現，生產新一代＂擬人化＂魚鱗，實為有效的解決之道，也是廠商急需提早佈局的專利技術之一。擬人化動物模式是將人類的基因、細胞或組織成功轉移至實驗動物，讓實驗動物帶有人類的細胞或表現人類的基因使實驗成果能更有效應用於人類。目前有些成功擬人化動物模式運用在疾病的研究，如Hematolymphoid humanized mice 及Humanized liver model 等。本計畫之目標在於利用基因轉殖與CRISPR/Cas 9 基因剔除技術，建立只表現人類膠原蛋白1A1 及1A2 之擬人化吳郭魚鱗，生產可做為人工生物眼角膜開發之吳郭魚擬人化魚鱗，完成後，將進行鱗片結構分析及進行進一步動物試驗，未來將技轉給柏登生醫進行臨床測試。 It has been estimated that up to 10 million in the world people suffer corneal blindness. Only 100,000 corneal transplants are performed each year worldwide due to the lack of access to donor tissue. Because of the defects of surgery with allogeneic donor corneal, such as transplant rejection, low operation success rates, or low donor corneal quality, scientists have tried to create an artificial cornea. But only few artificial cornea products available until now, a batter artificial cornea still have to be exploited. A research published in the Science Translational Medicine showed that collagen based biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage. The Body Organ Biomedical Corporation has developed the first type of bio-cornea from tilapia scales, and transplanted into rat and rabbit, the results are positive, but this may cause immune rejection in human transplantation in future clinical application. Therefore, the company tries to resolve this potential problem. A new generation of “Humanized” scale is an effective solution and could be the best product for clinical usage. Humanized animal models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research, such as hematolymphoid humanized mice and humanized mouse liver model. In this proposal, we will transfer human collagen 1A1 and 1A2 genes into tilapia and knock-out fish collagen 1A1 and 1A2 genes by CRISPR/Cas 9 technology to obtain a humanized tilapia expressing human collagen in the scales for artificial cornea production.

Keyword(s)

人工眼角膜
魚鱗
人類膠原蛋白質1A1/1A2
基因轉殖
基因剔除
artificial cornea
fish scale
human collagen 1A1/1A2
transgenic
knock-out

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Development of the New Generation Humanize Bio-Cornea (I)-3

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