Development of a novel fusogenic viral liposome system (HVJ-liposomes) and its applications to the treatment of acquired diseases.
Toward human gene therapy and gene analysis in vivo, a novel hybrid vector based on liposome has been developed for more efficient gene delivery and gene expression. The liposome was decorated with HVJ (Sendal virus) envelope fusion proteins to introduce DNA directly into the cytoplasm, and contained DNA and DNA-binding nuclear protein to enhance expression of the gene. Recently, several types of HVJ-liposomes were developed by altering the lipid components of the liposomes. HVJ-cationic liposomes increased gene delivery 100-800 times more efficiently in vitro than the conventional HVJ-anionic liposomes. HVJ-cationic liposomes were also more useful for gene expression in restricted portions of organs and for gene therapy of disseminated cancers. It was further discovered that the use of anionic liposomes with a virus-mimicking lipid composition (HVJ-AVE liposomes) increased transfection efficiency by several fold in vivo, especially in liver and muscle. By coupling the Epstein-Barr (EB) virus replicon apparatus to HVJ-liposomes, transgene expression was sustained in vitro and in vivo. Most animal organs were found to be suitable targets for the fusigenic-viral liposome system, and numerous gene therapy strategies using this system were successful in animals.
Kaneda
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Division of Gene Therapy Science, Osaka University School of Medicine, Japan. kaneday@imcb.osaka-u.ac.jp
D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D008954:Models, Biological; D018108:Respirovirus; D013997:Time Factors
D008081:Liposomes