NOVEL NON-VIRAL VECTOR USING BIODEGRADABLE THERMO-SENSITIVE POLYMER (ReGel? IN THE GENE THERPY OF ERECTILE DYSFUNCTION

초록

INTRODUCTION AND OBJECTIVES: ReGel? water-soluble biodegradable triblock copolymer (PEG-PLGA-PEG: poly-[ethylene glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol]), has recently been applied to gene therapy in several diseases. We investigated the feasibility of ReGel?as a carrier for controlled plasmid cDNA release in the corpus cavernosum. MATERIALS AND METHODS: To evaluate the transfection efficacy of ReGel?in normal corpus cavernosum, the Sprague-Dawley rats (250 ?300 g) were intracavernously injected with reporter gene, luciferase cDNA, either as naked plasmid cDNA (100 ug/0.1 ml, n=32), or plasmid cDNA complexed with 10% ReGel?(100 ug/0.1 ml, n=32) or 23% ReGel?(100 ug/0.1 ml, n=32). Cavernous tissue was harvested at 1, 3, 5, 10, 15 and 30 days after injection, and luciferase activity was measured. To evaluate the efficacy of ReGel?in cavernous tissue in erectile dysfunction (ED), rats in which hypercholesterolemia was induced by feeding 4% cholesterol diet for 3 months were injected intracavernously with either saline, or 23% ReGel? Luciferase gene, or 23% ReGel?+ VEGF165 gene. Erectile function was evaluated with cavernous nerve stimulation at 4 weeks postinjection in those rats. RESULTS: In the cavernous transfection assay in normal rats, luciferase activity was significantly higher in 23% ReGel?group than naked plasmid cDNA group or 10% ReGel?group. This effect was lasted up to 30 days postinjection. In the erectile function assay of hypercholesterolemic rats, 23% ReGel?+ VEGF group showed significantly increased maximal intracavernous pressure compared to control, or 23% ReGel?+ Luciferase group (p<0.05). CONCLUSIONS: We first report ReGel? as a non-viral vector, is a promising platform for delivery of plasmid cDNA, which may contribute to future gene therapy in ED.