| Budget Amount *help |
¥22,100,000 (Direct Cost: ¥22,100,000)
Fiscal Year 1998: ¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 1997: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Research Abstract |
Organ transplantation is a clinical strategy for terminal organ diseases due to the development of both immunsuppression and organ preservation. However, the donor shortage is a serious problem, followed by the necessity of xenotransplantation. It is well known that xenotransplantation has a immunologically great obstacle, which is called hyperacute rejection, and the conventional immunosuppressive therapy can not inhibit this type of rejection. To break through the limitation of both conventional immunosuppression and conventional preservation technique, we examined the effect of gene therapy technique on organ transplantation.
1) Using adenovirus-mediated gene transfer with CTLA4Ig cDNA, the gene expression period was maintained for several months, and the second administration of the vector was susceptible. In allotransplantation model of rats, the graft rejection was inhibited by this vector transfer via systemic route, which was followed by the graft acceptance. In concordant xenot
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ransplantation model of hamster-to-rat, the grafts survival was prominently prolonged in the combination with both this gene transfer and FK506.2) Using adenovirns-mediated gene transfer with alpha (1, 2) fucosyltransferase (FT) cDNA, the expression of alpha (1, 3) galactosyltransferase (GT) gene was down-regulated and the hyperacute rejection reaction was suppressed in xenotransplantation model. 3) Using adenovirus-mediated gene transfer with interleukin 1O (IL1O) , the ischemia-reperfusion injury was inhibited in the liver and the bacterial peritonitis was suppressed. 4) Using adenovirus-mediated gene transfer with interleukin 12 (IL12) cDNA, the multiple hepatic cancer or hepatic metastasis was suppressed in combination with anti-cancer drug.
These results demonstrated that the adenovirus-mediated gene transfer techniques were feasible for organ transplantation. To construct the gene transfer vector with organ-specific and tissue-specific characters, we examined the effect of the novel adenoviral vector with 20 residues of resin on the end of fiber-knob. Using this vector, we demonstrated the transduction eficiency with 20 to 50 folds, compared with the conventional vector. Less
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