Author(s): Lee ES, Rasmussen CA, Filla MS, Slauson SR, Kolb AW,Peters DM,Kaufman PL, Gabelt BT, Brandt CR. Prospects for lentiviral vector mediated prostaglandin F synthase gene delivery in monkey eyes in vivo. Curr Eye Res. 2014 Sep;39(9):859-70. doi: 10.3109/02713683.2014.884593. Epub 2014 Feb 21. Review.
Journal: Current Eye Research, Volume 39, Issue 9, Sep 2014
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.