Effect of RNA interference on Gal alpha 1,3 Gal expression in PIEC cells.
Xenotransplantation from pig to human being is viewed as a potential solution for the acute organ shortage. However, consequent xenorejection induced by Gal alpha 1,3 Gal (Gal, Gal antigen) prevents xenotransplantation from clinical application. Thus, the most attracting attempt to prevent xenorejection is the elimination of Gal. Our study suggested that compared with the human alpha 1,2 fucosyltransferase (FT) gene and porcine antisense alpha 1,3 galactosyltransferase gene, sequence-specific siRNA targeting Gal were capable of suppressing Gal expression markedly, and therefore, significantly inhibiting xenoreactivity and the complement activation with human serum in PIEC cells. We also demonstrated the concordant inhibitory effect of siRNA and human FT gene on Gal and corresponding functions, which implied a practical significance of combined transgenic strategy. The successful application of vector-based dsRNA-GT may extend the list of available modalities in the abrogation of xenorejection in xenotransplantation.
Yu
Luyang
L
Graduate School of the Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Miao
Hongsheng
H
Guo
Lihe
L
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003176:Complement C3 / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004187:Disaccharides / Q000378:metabolism*; D004730:Endothelium, Vascular; D005700:Galactosyltransferases / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology*; D013552:Swine; D014162:Transfection
D003176:Complement C3; D004187:Disaccharides; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; C055075:galactosyl-(1-3)galactose; D049452:Green Fluorescent Proteins; D005700:Galactosyltransferases