title: Prospects for lentiviral vector mediated prostaglandin F synthase gene delivery in monkey eyes in vivo.
abstract: Currently, the most effective outflow drugs approved for clinical use are prostaglandin F2α analogues, but these require daily topical self-dosing and have various intraocular, ocular surface and extraocular side effects. Lentiviral vector-mediated delivery of the prostaglandin F synthase (PGFS) gene, resulting in long-term reduction of intraocular pressure (IOP), may eliminate off-target tissue effects and the need for daily topical PGF2α self-administration. Lentiviral vector-mediated delivery of the PGFS gene to the anterior segment has been achieved in cats and non-human primates. Although these results are encouraging, our studies have identified a number of challenges that need to be overcome for prostaglandin gene therapy to be translated into the clinic. Using examples from our work in non-human primates, where we were able to achieve a significant reduction in IOP (2 mm Hg) for 5 months after delivery of the cDNA for bovine PGF synthase, we identify and discuss these issues and consider several possible solutions.
authors.affiliation: Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine , Seoul , Korea .
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Lee
authors.forename: Carol A
authors.initials: CA
authors.lastname: Rasmussen
authors.forename: Mark S
authors.initials: MS
authors.lastname: Filla
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Slauson
authors.forename: Aaron W
authors.initials: AW
authors.lastname: Kolb
authors.forename: Donna M
authors.initials: DM
authors.lastname: Peters
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kaufman
authors.forename: B'Ann T
authors.initials: BT
authors.lastname: Gabelt
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Brandt
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D005901:Glaucoma / Q000628:therapy; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics*; D007429:Intraocular Pressure; D016086:Lentivirus / Q000235:genetics*; D008251:Macaca
chemical_list: D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase
keywords: Glaucoma; gene therapy; lentivirus; prostaglandin synthase; trabecular meshwork