Effect of RNA interference on Gal alpha 1,3 Gal expression in PIEC cells.
Xenotransplantation from pigs to human beings is viewed as a potential solution for the acute organ shortage. However, consequent xenorejection induced by Gal alpha 1,3 Gal (a 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 the porcine antisense alpha 1,3 galactosyltransferase gene, sequence-specific siRNA targeting Gal was 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 the 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
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Miao
Hongsheng
H
Guo
Lihe
L
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003124:Colorimetry; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D017931:DNA Primers; D004187:Disaccharides / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D005697:Galactosides; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007211:Indoles; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034421:Sus scrofa; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D014183:Transplantation, Heterologous / Q000379:methods*
D017931:DNA Primers; D004187:Disaccharides; D005697:Galactosides; D007211:Indoles; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; C055075:galactosyl-(1-3)galactose; D005647:Fucosyltransferases; D005700:Galactosyltransferases; C022616:thiazolyl blue; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside