Differences in gene expression between sonoporation in tumor and in muscle

Abstract

Ultrasound (US) is a novel and effective tool for the local delivery of genes into target tissues. US can temporarily change the permeability of a cell membrane and thus enhance the delivery of naked DNA into cells. In the present study, the efficiencies of gene expression mediated by US delivery in orthotopic liver tumor, subcutaneous tumor and muscle tissue were evaluated by changing the contrast agent concentrations and US exposure durations. Plasmid DNA coding for luciferase, interleukin-12 or enhanced green fluorescence protein was mixed with SonoVue and injected intratumorally or intramuscularly. The injection sites were then exposed to US (20% duty cycle and 0.4 W/cm(2) intensity). The results obtained showed that the optimal condition was 50% SonoVue for tumors and 30% for muscle, with 10 min of US exposure. The expression levels of the transfected DNAs were in the order: muscle > subcutaneous tumor > orthotopic liver tumor. The present study indicates that muscle tissue is a good target site for producing large amounts of gene products for the purpose of gene therapy.