Burlak C, Paris L L, Lutz A J, Sidner R A, Estrada J, Li P, Tector M, Tector A J
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.
Am J Transplant. 2014 Aug;14(8):1895-900. doi: 10.1111/ajt.12744. Epub 2014 Jun 6.
Xenotransplantation using genetically modified pig organs could solve the donor organ shortage problem. Two inactivated genes that make humans unique from pigs are GGTA1 and CMAH, the products of which produce the carbohydrate epitopes, aGal and Neu5Gc that attract preformed human antibody. When the GGTA1 and CMAH genes were deleted in pigs, human antibody binding was reduced in preliminary analysis. We analyzed the binding of human IgM and IgG from 121 healthy human serum samples for binding to GGTA1 KO and GGTA1/CMAH KO peripheral blood mononuclear cells (PBMCs). We analyzed a sub population for reactivity toward genetically modified pig PBMCs as compared to chimpanzee and human PBMCs. Deletion of the GGTA1 and CMAH genes in pigs improved the crossmatch results beyond those observed with chimpanzees. Sorting the 121 human samples tested against the GGTA1/CMAH KO pig PBMCs did not reveal a distinguishing feature such as blood group, age or gender. Modification of genes to make pig carbohydrates more similar to humans has improved the crossmatch with human serum significantly.
使用基因编辑猪器官进行异种移植可以解决供体器官短缺问题。使人类区别于猪的两个失活基因是GGTA1和CMAH，它们的产物产生碳水化合物表位αGal和Neu5Gc，这些表位会吸引预先形成的人类抗体。当猪体内的GGTA1和CMAH基因被删除后，初步分析显示人类抗体结合减少。我们分析了121份健康人血清样本中的人类IgM和IgG与GGTA1基因敲除（KO）和GGTA1/CMAH双基因敲除的外周血单核细胞（PBMC）的结合情况。我们分析了一个亚群对基因编辑猪PBMC的反应性，并与黑猩猩和人类PBMC进行比较。猪体内GGTA1和CMAH基因的缺失改善了交叉配型结果，超过了在黑猩猩身上观察到的结果。对121份针对GGTA1/CMAH双基因敲除猪PBMC进行检测的人类样本进行分类，未发现血型、年龄或性别等显著特征。对基因进行改造以使猪的碳水化合物更接近人类，显著改善了与人类血清的交叉配型。
