Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys

doi:10.1016/j.ymthe.2019.04.021

CORC > 成都生物研究所 > 中国科学院成都生物研究所 > 国家天然药物工程技术研究中心 > 天然产物研究

	Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys
	Tan, Junkai 5,6; Liu, Guo 5; Zhu, Xianjun 3,4; Wu, Zhijian 2; Wang, Ningli 1; Zhou, Liang 4; Zhang, Xiaoguang 5; Fan, Ning 5; Liu, Xuyang 5,6
刊名	MOLECULAR THERAPY
	2019
卷号	27 期号:7 页码:1327-1338
ISSN号	1525-0016
DOI	10.1016/j.ymthe.2019.04.021
产权排序	4
文献子类	Article
英文摘要	Primary open-angle glaucoma (POAG) is considered a lifelong disease characterized by optic nerve deterioration and visual field damage. Although the disease progression can usually be controlled by lowering the intraocular pressure (IOP), therapeutic effects of current approaches do not last long. Gene therapy could be a promising method for persistent treatment of the disease. Our previous study demonstrated that gene transfer of exoenzyme C3 transferase (C3) to the trabecular meshwork (TM) to inhibit Rho GTPase (Rho), the upstream signal molecule of Rho-associated kinase (ROCK), resulted in lowered IOP in normal rodent eyes. In the present study, we show that the lentiviral vector (LV)-mediated C3 expression inactivates RhoA in human TM cells by ADP ribosylation, resulting in disruption of the actin cytoskeleton and altered cell morphology. In addition, intracameral delivery of the C3 vector to monkey eyes leads to persistently lowered IOP without obvious signs of inflammation. This is the first report of using a vector to transduce the TM of an alive non-human primate with a gene that alters cellular machinery and physiology. Our results in non-human primates support that LV-mediated C3 expression in the TM may have therapeutic potential for glaucoma, the leading cause of irreversible blindness in humans.
学科主题	Biology
URL标识	查看原文
WOS关键词	HUMAN TRABECULAR MESHWORK ; INDUCED OCULAR HYPERTENSION ; INCREASES OUTFLOW FACILITY ; DOMINANT-NEGATIVE RHOA ; GENE-TRANSFER ; TRANSGENE EXPRESSION ; KINASE INHIBITOR ; ANTERIOR SEGMENT ; ROCK INHIBITOR ; LATRUNCULIN-A
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000473731900012
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/31058]
专题	国家天然药物工程技术研究中心_天然产物研究
通讯作者	Liu, Xuyang
作者单位	1.Capital Med Univ, Beijing Tongren Hosp, Tongren Eye Ctr, Beijing, Peoples R China 2.NEI, Ocular Gene Therapy Core, NIH, 6 Ctr Dr,Room 307, Bethesda, MD 20892 USA; 3.Chinese Acad Sci, Sichuan Translat Med Res Hosp, Chengdu Inst Biol, Chengdu, Sichuan, Peoples R China; 4.Prov Peoples Hosp, Sichuan Acad Med Sci, Inst Lab Anim Sci, Chengdu, Sichuan, Peoples R China; 5.Shenzhen Univ, Sch Optometry, Shenzhen Eye Hosp, Shenzhen Key Lab Ophthalmol, Shenzhen, Peoples R China; 6.Xiamen Univ, Xiamen Eye Ctr, 336 Xiahe Rd, Xiamen 361001, Fujian, Peoples R China;
推荐引用方式 GB/T 7714	Tan, Junkai,Liu, Guo,Zhu, Xianjun,et al. Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys[J]. MOLECULAR THERAPY,2019,27(7):1327-1338.
APA	Tan, Junkai.,Liu, Guo.,Zhu, Xianjun.,Wu, Zhijian.,Wang, Ningli.,...&Liu, Xuyang.(2019).Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys.MOLECULAR THERAPY,27(7),1327-1338.
MLA	Tan, Junkai,et al."Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys".MOLECULAR THERAPY 27.7(2019):1327-1338.