Enhanced Expressions and Histological Characteristics of Intravenously Administered Plasmid DNA in Rat Lung

Abstract

INTRODUTIONIntravenous delivery of therapeutic genes for gene therapy has an advantage for lung tumor that is deeply located in the thorax. But there are few successful methods for intravenous delivery of genes into the lung. Several methods using viral (1, 2) and liposomal (3-7) vectors are now studied intensively for intravenous delivery of genes into the lung. Templeton et al. (6) demonstrated that DOTAP-cholesterol-plasmid DNA complex showed high affinity in mouse lung after intravenous infusion. DOTAP is a well-known cationic lipid for making lipid-DNA complex and is used in many gene transfection researches. Recently, the ability for intravenously administered naked plasmid DNA to be expressed at substantial levels in mammalian organs was demonstrated (8-10). Also several supportive methods for enhancement of intravenously administered naked plasmid DNA transfection were introduced. Song et al. (9) demonstrated that intravenously pretreated DOTAP, which formed transient microembolism on pulmonary capillary beds, prolonged the retention time of naked plasmid DNA and produced more transfection efficiency of plasmid DNA. Liu et al. (10) demonstrated that rapid intravenous injection of a large volume of naked plasmid DNA solution produced efficient gene transfection. In this study, we have compared the transfection efficiencies and histological characteristics after intravenous administration 1) of naked plasmid DNA alone, 2) naked plasmid DNA after DOTAP pretreatment, and 3) DOTAPcholesterol-plasmid DNA complex.