Abstract
Today nonviral gene transfer vectors attract more attention as a therapeutic strategy for human diseases, because viral vectors have problems, especially in immunogenicity and cytotoxicity. However, main limitation of nonviral vectors has been low efficiency of gene expression. To overcome this defect, we have developed a new class of gene transfer system, HVJ-cationic liposomes. The use of cationic lipid, DC-cholesterol, facilitates efficient entrapment of negatively charged macromolecules and efficient interaction with negatively charged plasma membrane. Moreover, the fusogenic envelope proteins of HVJ enhance delivery of genes and oligonucleotides. We have succeeded in obtaining 100-800 times higher gene expression than the conventional HVJ-liposome method. On the other hand, although several gene transfer methods have been utilized in clinical gene therapy trials, there is no almighty method. Thinking of problems in all methods including nonviral methods, the one thing that is common in all methods is we cannot target the specific organ or area. To improve the specificity of gene transfer we have succeeded in developing an immunoliposome (HVJ-liposome + Anti Thy 1 antibody). With this newly developed method, we performed specific gene transfer into the kidney especially to glomeruli. Taken together we have developed a novel nonviral vector system based on HVJ-liposome method.
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