Intratumoral Injection of Naked DNA

Direct injection of naked DNA into tissues as a gene-delivery method has been extensively studied for genetic immunization and gene therapy ( 1 ). When naked plasmid DNA was used as a negative control while cationic liposomes were studied, it was surprisingly found that direct injection of naked DNA into skeletal muscle resulted in higher gene expression than injection of cationic liposomes ( 2 ). Naked DNA was reported as more efficient than retroviral and adenoviral vectors following direct injection into adult mouse skeletal muscle ( 3 ). Subsequently, cardiac muscles, thyroid, joint, liver, lung, brain, kidney, as well as solid tumors were found capable of taking up and expressing naked DNA ( 4 - 10 ). In some tumors, gene expression following intratumoral injection of naked DNA was higher than that of DNA associated with cationic liposomes Fig. 1 ) ( 7 ). This is probably because of the faster dessimination rate of naked plasmid DNA in the tumor than that of DNA complexed with cationic liposomes (111).   Fig. 1.  CAT reporter gene expression in murine BL6 melanoma. pUCCMVCAT plasmid DNA was injected into the tumor. Mice were sacrificed 2 d later and tumor protein extracts were assayed for CAT activity. Lanes 16 and 17: 0.005 and 0.01 units of purified CAT standard enzyme, respectively. Lane 18: extracts from tumors injected with 5% glucose only [with the permission from ( 7 )].