Prolonged Transgene Expression with Lentiviral Vectors in the Aqueous Humor Outflow Pathway of Nonhuman Primates

被引:45
作者
Barraza, Roman A. [1 ]
Rasmussen, Carol A. [4 ]
Loewen, Nils [1 ]
Cameron, J. Douglas [2 ,3 ]
Gabelt, B'Ann T. [4 ]
Teo, Wu-Lin [1 ]
Kaufman, Paul L. [4 ]
Poeschla, Eric M. [1 ]
机构
[1] Mayo Clin, Coll Med, Dept Mol Med, Rochester, MN 55905 USA
[2] Mayo Clin, Coll Med, Dept Ophthalmol, Rochester, MN 55905 USA
[3] Mayo Clin, Coll Med, Dept Anat Pathol, Rochester, MN 55905 USA
[4] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53792 USA
关键词
FELINE IMMUNODEFICIENCY VIRUS; KINASE INHIBITOR Y-27632; OPEN-ANGLE GLAUCOMA; INTRAOCULAR-PRESSURE; TRABECULAR MESHWORK; GENE-TRANSFER; CULTURED HUMAN; LONG-TERM; FACILITY; MONKEY;
D O I
10.1089/hum.2008.086
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We injected lentiviral vectors into the eyes of live nonhuman primates to assess potential for glaucoma gene therapy. Anterior chambers of five cynomolgus monkeys were injected with green fluorescent protein (GFP)encoding feline immunodeficiency viral vectors. The monkeys were monitored for in vivo transgene expression and clinical parameters. Their eyes were harvested 2-15 months postinjection for tissue analyses. All seven eyes injected with 1.0-2.0x10(8) transducing units (TU) showed substantial GFP fluorescence in the trabecular meshwork (TM), which was observable even by goniophotographic monitoring for up to 15 months. Only the lowest dose (0.03x10(8) TU) failed to result in TM fluorescence detectable in vivo, and five of the eight vector-injected eyes continued to display substantial GFP expression when enucleated eyes were examined at 2, 7, or 15 months postinjection. Some transduced cells were also detected in the iris and ciliary body. Mild, transient postinjection inflammatory responses exceeding that induced by a control saline injection were observed, but vectors did not raise intraocular pressure and were well tolerated. The results demonstrate the first lentiviral vector transduction of the nonhuman primate aqueous humor outflow pathway and support application of the system to human glaucoma gene therapy.
引用
收藏
页码:191 / 200
页数:10
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