Introduction of plasmid DNA and oligonucleotides into lung epithelial cells by the hemagglutinating virus of Japan (HVJ)-liposome method

The hemagglutinating virus of Japan (HVJ) fused with liposomes provides a u nique transfection vehicle with characteristics of both virus vector and li posome. Here we investigate the efficiency and safety of the HVJ-liposome t echnique in delivering foreign genes and oligonucleotides into the lung of the Wistar rat. A plasmid vector containing the Escherichia coli beta-galac tosidase (beta-gal) gene and the chicken beta-actin promoter was transfecte d via the trachea using the HVJ-liposome method. Cytochemical staining show ed expression of exogenous beta-gal activity in airway epithelial cells, al veolar macrophages, and alveolar type II cells. This activity persisted at least 28 days after administration of the genes. FITC-labeled oligonucleoti des also were introduced into the same types of lung cells as those express ing beta-gal. After instillation of HVJ-liposome, anti-HVJ antibodies were detected in the sera of the rats, but even after repeated administration of HVJ-liposome, no marked histopathologic change was observed while exogenou s beta-gal expression was detected in pulmonary cells.