Gene Expression Following Direct Injection of DNA into Liver

ABSTRACT The liver is an attractive target tissue for gene therapy. Current approaches for hepatic gene delivery include retroviral and adenoviral vectors, liposome/DNA, and peptide/DNA complexes. This study describes a technique for direct injection of DNA into liver that led to significant gene expression. Gene expression was characterized in both rats and cats following injection of plasmid DNA encoding several different proteins. Luciferase activity was measured after injection of plasmid DNA encoding the luciferase gene (pCMVL), β-galactosidase (β-Gal) activity was evaluated in situ using plasmid DNA encoding Lac Z (pCMVβ), and serum concentration of secreted human α-1-antitrypsin was measured following injection of plasmid DNA encoding this protein (pRC/CMV-sHAT). Several variables, including injection technique, DNA dose, and DNA diluent, were investigated. Direct injection of pCMVL resulted in maximal luciferase expression at 24–48 hr. β-Gal staining demonstrated that the majority of transfected h...