Antigenicity of tissues and organs from GGTA1/CMAH/β4GαlNT2 triple gene knockout pigs
Ronggen Wang
Miaomiao Ruan
Runjie Zhang
Lei Chen
Xiaoxue Li
Bin Fang
Chu Li
Xueyang Ren
Jiying Liu
Qiang Xiong
Lining Zhang
Yong Jin
Lin Li
Rongfeng Li
Ying Wang
Haiyuan Yang
Yifan Dai
摘要：Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts.To overcome biological incompatibility between pigs and humans,one strategy is to remove the major antigens [Gal,Neu5Gc,and Sd(a)] present on pig cells and tissues.Triple gene (GGTA1,CMAH,and β4GalNT2) knockout (TKO) pigs were produced in our laboratory by CRISPR-Cas9 targeting.To investigate the antigenicity reduction in the TKO pigs,the expression levels of these three xenoantigens in the cornea,heart,liver,spleen,lung,kidney,and pancreas tissues were examined.The level of human IgG/IgM binding to those tissues was also investigated,with wildtype pig tissues as control.The results showed that αGal,Neu5Gc,and Sd(a) were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs.Compared to wildtype pigs,the liver,spleen,and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding,whereas corneas,heart,lung,and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding.These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach.
机标关键词：
分类号：R392.4(医学免疫学)
资助基金：grants from the National Natural Science Foundation of China(81570402 & 31701283)the National Key R&D Program of China(2017YFC1103701 & 2017YFC1103702)the Jiangsu Key Laboratory of Xenotransplantation(BM2012116)the Sanming Project of Medicine in Shenzhen,the Fund for High Level Medical Discipline Construction of Shenzhen(2016031638)the Shenzhen Foundation of Science and Technology(JCYJ20160229204849975 & GCZX2015043017281705)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 235-243 )
英文信息