Indexed on: 26 Oct '05Published on: 26 Oct '05Published in: Advances in genetics
To create a highly efficient vector system that is minimally invasive, we initially developed liposomes that contained fusion proteins from the hemagglutinating virus of Japan (HVJ; Sendai virus). These HVJ-liposomes delivered genes and drugs to cultured cells and tissues. To simplify the vector system and develop more efficient vectors, the next approach was to convert viruses to non-viral vectors. Based on this concept, we recently developed the HVJ envelope vector. HVJ with robust fusion activity was inactivated, and exogenous DNA was incorporated into the viral envelope by detergent treatment and centrifugation. The resulting HVJ envelope vector introduced plasmid DNA efficiently and rapidly into both cultured cells in vitro and organs in vivo. Furthermore, proteins, synthetic oligonucleotides, and drugs have also been effectively introduced into cells using the HVJ envelope vector. The HVJ envelope vector is a promising tool for both ex vivo and in vivo gene therapy experiments. Hearing impairment in rats was prevented and treated by hepatocyte growth factor gene transfer to cerebrospinal fluid using HVJ envelope vector. For cancer treatment, tumor-associated antigen genes were delivered efficiently to mouse dendritic cells to evoke an anti-cancer immune response. HVJ envelope vector fused dendritic cells and tumor cells and simultaneously delivered cytokine genes, such as IL-12, to the hybrid cells. This strategy successfully prevented and treated cancers in mice by stimulating the presentation of tumor antigens and the maturation of T cells. For human gene therapy, a pilot plant to commercially produce clinical grade HVJ envelope vector has been established.
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