Transformed pig in which HO-1 gene and TNFR1-Fc gene are simultaneously expressed and GGTA1 gene is knocked out, and use thereof

摘要

The present invention simultaneously expresses a HO-1 (Heme oxygenase-1) gene and a TNFR1-Fc (Tumor necrosis factor receptor 1-Fc) gene, and a GGTA1 (α-1,3-galactosyltransferase) gene is knocked out ( The present invention relates to a transformed pig that is knocked out and in which immune rejection at the time of xenotransplantation is suppressed, and a method for producing the same. A transformed pig in which the human HO-1 and TNFR1-Fc fusion gene of the present invention is simultaneously expressed and the GGTA1 gene is knocked out is separated into organs by the antioxidant action or cytoprotective function of the HO-1 gene. Oxidative stress can be reduced during in vitro culture, TNFR1-Fc expression can also reduce TNF-α-mediated inflammatory responses that occur early in transplantation, and suppress dendritic cell maturation and increase T cell proliferation and By regulating activation, acute vascular rejection can be reduced and early engraftment of transplanted organs can be promoted. Furthermore, the survival rate of the transplanted organ can be improved by suppressing hyperacute rejection by GGTA1. Therefore, an organ in which immune rejection at the time of xenotransplantation is suppressed can be produced using the transformed pig.