We have combined hemagglutinating virus of Japan (HVJ; Sendai virus) with
liposomes for efficient in vitro and in vivo fusion-mediated gene delivery. The HVJ-
liposome was a highly efficient vehicle for the introduction of
oligonucleotides into cells in vivo as well as for the transfer of genes <100 kbp without damaging cells. By coupling the Epstein-Barr (EB) virus replicon apparatus with HVJ-
liposomes (
virosomes), transgene expression was sustained in vitro and in vivo. When we added cationic
lipids, the HVJ-cationic
liposomes increased gene delivery 100 to 800 times in vitro compared with the conventional anionic
virosomes and were also more useful for gene expression in restricted areas of organs and for gene therapy of disseminated
cancers. We further discovered that the use of anionic
virosomes with a virus-mimicking
lipid composition (artificial viral envelope; AVE type) increased transfection efficiency approximately 10 fold in vivo, especially in the heart, liver, kidney, and muscle. Most animal organs were found to be suitable targets for the fusigenic
virosomes, and numerous gene therapy strategies using this system were successful in animals. The combination of suicide gene therapy with radiation was very effective for killing
hepatomas in a mouse model.
Arteriosclerosis obliterans in animal models was cured by the transfer of
hepatocyte growth factor.