Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach.\nThe eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune\nand inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and\nevaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic\nretinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented\nepithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds\nand coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the\nliposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex\nformulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE\ncells and a GFP-encoding plasmid.The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to\nthe known lipid references 3????-[N-(N????,N????-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-\n3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA\ncarriers for ocular gene therapy.
Loading....