Systemic Administration of Naked DNA: Gene Transfer to Skeletal Muscle

Efficacy of transgene expression in the mouse diaphragm following circulatory occlusion.

A. Circulatory occlusion greatly enhances gene transfer. Blood flow through the diaphragm was blocked (4 s) immediately following intravenous injection of plasmid DNA (80 mg in 100 ml of saline solution) containing a gene for luciferase. The level of gene expression (relative light units per mg of total protein extracted from tissue) was determined one day after injection.

B. Expression of transgene over time. Levels of luciferase activity attained through circulatory occlusion dropped off logarithmically over the two-month period following treatment to reach a value that persisted until at least six months after treatment. The level of gene expression in other organs including the liver, lung, heart, spleen, and kidney was undetectable at day six after administration.