Antigenicity of tissues and organs from GGTA1/CMAH/β4GalNT2 triple gene knockout pigs

查看全文 作　　者：Ronggen [1]Wang;Miaomiao [1]Ruan;Runjie [1]Zhang;Lei [1]Chen;Xiaoxue [1]Li;Bin [1]Fang;Chu [1]Li;Xueyang [1]Ren;Jiying [1]Liu;Qiang [1]Xiong;Lining [1]Zhang;Yong [1]Jin;Lin [1,2]Li;Rongfeng [1,2]Li;Ying [1,2]Wang;Haiyuan [1,2]Yang;Yifan [1,2,3,4]Dai

机构地区：[1]Jiangsu Key Laboratory of Xenotransplantation;[2]Key Laboratory of Targeted Intervention of Cardiovascular Disease,Collaborative Innovation Center for Cardiovascular Disease Translational Medicine;[3]State Key Laboratory of Reproductive Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China;[4]Shenzhen Xenotransplantation Medical Engineering Research and Development Center,Institute of Translational Medicine,Shenzhen Second People rs Hospital,First Affiliated Hospital of Shenzhen University,Shenzhen,Guangdong 518035,China.

出　　处：《The Journal of Biomedical Research》索引2019年第33卷第4期,共9页

基　　金：supported by 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) 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,Neu5 Gc,and Sd(a)]present on pig cells and tissues.Triple gene(GGTAI,CMAH,and β4 GalNT2)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 aGal,Neu5 Gc,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. 关键词：PIG XENOTRANSPLANTATION GGTA1 CMAH β4GaINT2 ANTIGENICITY

相关文献

参考文献（31）
引证文献（5）
耦合文献（0）

参考文献(31)

引证文献(5)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

Antigenicity of tissues and organs from GGTA1/CMAH/β4GalNT2 triple gene knockout pigs

参考文献(31)

引证文献(5)

用户提示