Miyagawa S, Tanemura M, Koyota S, Koma M, Ikeda Y, Shirakura R, Taniguchi N
Department of Biochemistry, Division of Organ Transplantation, Biomedical Research Center, Osaka University Medical School, Osaka, Japan.
Biochem Biophys Res Commun. 1999 Nov 2;264(3):611-4. doi: 10.1006/bbrc.1999.1327.
The alpha-Gal epitope (Gal-alpha1-3Gal-beta1-4-GlcNAc-R), which is biosynthesized by the UDP-Gal:alpha1-3-galactosyltransferase (alpha1, 3GT), is highly associated with hyperacute rejection in swine to human xenotransplantation. A variety of strategies have been pursued to reduce or eliminate this epitope from swine tissues. Since swine ES cells are not available at present, the targeted knock out of the alpha1,3GT is restricted. Other strategies, such as enzyme competition of the alpha1,3GT with other glycosyltransferases and/or control of sugar processing by the glycosyltransferases, provide a new insight into the downregulation of the alpha-Gal epitope. This review will focus on this type of strategy, which involves a gene transfection of variety of glycosyltransferases as competitors against alpha1,3GT.
α - 半乳糖表位(Gal-α1-3Gal-β1-4-GlcNAc-R)由UDP - Gal:α1-3 - 半乳糖基转移酶(α1, 3GT)生物合成,与猪到人类异种移植中的超急性排斥反应高度相关。人们已经采用了多种策略来减少或消除猪组织中的这种表位。由于目前无法获得猪胚胎干细胞,α1,3GT的靶向敲除受到限制。其他策略,如α1,3GT与其他糖基转移酶的酶竞争和/或糖基转移酶对糖加工的控制,为下调α - 半乳糖表位提供了新的思路。本综述将聚焦于这类策略,该策略涉及转染多种糖基转移酶基因作为α1,3GT的竞争剂。