[Development of in vivo gene transfer methods towards future gene therapy].
More than 100 protocols have been proposed for human gene therapy in the United States, but no effective results have been reported in the gene therapy field. This failure in gene therapy mainly results from the lack of effective gene transfer vectors. As far as somatic gene therapy is concerned, it will be very hard to control systemic disorders even after a much more powerful vector system is developed. However, local disorders will be able to be better regulated by gene therapy. In this regard, cardiovascular diseases will be suitable and promising targets for future gene therapy. Fusigenic viral-liposome, called HVJ-liposome, seems to be an effective tool for gene therapy. In this system, genes, oligonucleotides and proteins can be directly introduced into the cytoplasm by virus-cell fusion. Using HVJ-liposome, restenosis after angioplasty was successfully prevented in rat carotid artery by the introduction of either antisense oligonucleotides against cell-cycle controlling factor or double-stranded oligonucleotides containing E2F binding sites as a decoy. Constitutive nitric oxide synthase gene was also effective in inhibiting of neointima formation in rat carotid artery. These results indicate the possibility of gene therapy to prevent restenosis after angioplasty. We present here novel targets for future gene therapy.
Kaneda
Y
Y
Institute for Molecular and Cellular Biology, Osaka University, Suita.
Morishita
R
R
D017130:Angioplasty; D000818:Animals; D002318:Cardiovascular Diseases / Q000628:therapy; D016893:Carotid Stenosis / Q000517:prevention & control; D002459:Cell Fusion; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes; D019001:Nitric Oxide Synthase / Q000235:genetics; D016376:Oligonucleotides, Antisense; D051381:Rats; D012008:Recurrence; D018108:Respirovirus
D008081:Liposomes; D016376:Oligonucleotides, Antisense; D019001:Nitric Oxide Synthase