INTRALUMINAL WATER INCREASES EXPRESSION OF PLASMID DNA IN RAT LUNG

Effective gene delivery to specific organs is a major goal for human g ene therapy, The lung's structure allows instillation of agents into t he airspaces, directly adjacent to the lung epithelium. We hypothesize d that the airspace instillation of hypotonic solutions would increase the permeability of the lung epithelium and increase DNA uptake, This hypothesis was tested by instilling plasmid DNA (p4241) encoding the luciferase gene in isotonic and hypotonic solutions, The highest lucif erase expression in the lung was achieved after the instillation of th is plasmid DNA in distilled water, Aerosolization of water just before the instillation of the plasmid DNA also enhanced the expression leve l of luciferase in the lung, In addition, an intralobar instillation o f the plasmid DNA in water significantly increased the luciferase expr ession, suggesting that the instillation of the plasmid over a smaller surface area increased expression, Levels of expression could be meas ured for 3 days, Water increases the permeability of lung epithelial c ells transiently and/or enhances gene expression and can be used to ac hieve gene expression in the lung airspaces for short intervals withou t toxicity.