The Hemagglutinating Virus of Japan–Liposome Method for Gene Delivery

Abstract

Publisher Summary This chapter focuses on the construction of novel, hybrid-type liposomes with functional molecules inserted into them. DNA-loaded liposomes are fused with ultraviolet (UV) inactivated hemagglutinating virus of Japan (HVJ, Sendai virus) to form HVJ liposomes. Those viral liposomes bind to cell surface sialic acid receptors and fuse with cell membrane to directly introduce DNA into the cytoplasm without degradation. The HVJ–liposomes encapsulate DNA smaller than 100 kb. RNA, oligodeoxynucleotides (ODN), proteins, and drugs can also be enclosed and delivered to cells. By the use of fluorescence resonance energy transfer (FRET), the degradation of ODN in the process of delivery to the cytoplasm is inhibited by HVJ-liposomes but not with simple cationic liposomes. HVJ-liposomes are useful for in vivo gene transfer. When HVJ–liposomes containing the β-galactosidase (LacZ) gene were injected directly into one rat liver lobe, approximately 70% of cells expressed LacZ gene activity, and no pathological hepatic changes were observed. The safety of HVJ–liposomes has been tested and evaluated in monkeys. The lipid components of the liposomes are very similar to the HIV envelope and mimic the red blood cell membrane. Positively charged DC-cholesterol (DC) is most efficient for gene transfer. For luciferase expression, HVJ–cationic DC liposomes were 100 times more efficient than conventional HVJ–anionic liposomes.