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Abstract #23511 Published in IGR 11-2
Prolonged transgene expression with lentiviral vectors in the aqueous humor outflow pathway of nonhuman primates
Barraza RA; Rasmussen CA; Loewen N; Cameron JD; Gabelt BT; Teo W-L; Kaufman PL; Poeschla EMHuman Genetics and Therapeutics 2009; 20: 191-200
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 1.0-2.0 x 10(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 (0.03 x 10 (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.
E. M. Poeschla. Guggenheim 18, Mayo Clinic, College of Medicine, 200 First Street SW, Rochester, MN 55905, United States. emp@mayo.edu
Classification:
11.9 Gene therapy (Part of: 11 Medical treatment)
2.6.2.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics > 2.6.2 Outflow)
5.2 Primates (Part of: 5 Experimental glaucoma; animal models)
