Herpes simplex virus-enhanced cationic lipid/DNA-mediated transfection

Liposome plasmid DNA complexes (lipoplexes) are often inefficient in mediat ing gene transfer and expression because of DNA degradation in lysosomal ve sicles. Because herpes simplex virus (HSV) enters cells by fusion of the vi rus envelope with the plasma membranes, thereby overriding the endosomal pa thway, HSV/lipoplex mixtures could be useful for improving gene transfer pa rticularly when the mixture uses highly defective HSV particles that fail t o express cytotoxic viral gene products. To evaluate this possibility, lipo plexes composed of cationic liposomes and lacZ reporter plasmids were compa red for their ability to transduce cells in culture in the presence and abs ence of infectious HSV particles. The results showed that HSV increased the efficiency of cell transduction by approximately 4-100-fold compared with lipoplex vector alone, depending on the cell type targeted for gene deliver y. The increased efficiency of transduction was virus dose dependent and re quired virus entry.