DOI: 10.1002/ame2.12461
Elimination of GGTA1,CMAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions
Jing Xu1
Jilong Ren2
Kai Xu2
Minghui Fang3
Meina Ka1
Fei Xu3
Xin Wang1
Jing Wang1
Zhiqiang Han1
Guihai Feng2
Ying Zhang2
Tang Hai4
Wei Li5
Zheng Hu3
1.State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;Key Laboratory of Organ Regeneration and Reconstruction,Chinese Academy of Sciences,Beijing,China;University of Chinese Academy of Sciences,Beijing,China2.State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;Key Laboratory of Organ Regeneration and Reconstruction,Chinese Academy of Sciences,Beijing,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing,China3.Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education,The First Hospital,Jilin University,Changchun,China4.State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;Key Laboratory of Organ Regeneration and Reconstruction,Chinese Academy of Sciences,Beijing,China;Beijing Farm Animal Research Center,Institute of Zoology,Chinese Academy of Sciences,Beijing,China5.State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing,China;Key Laboratory of Organ Regeneration and Reconstruction,Chinese Academy of Sciences,Beijing,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing,China;University of Chinese Academy of Sciences,Beijing,China
摘要：Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to im-prove the immune compatibility between humans and pigs.Current knockout strat-egies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHC Ⅱ molecule plays critical roles.
Methods:Thus,we generate a 4-gene ( GGTA1,CMAH,β4GalNT2,and CIITA ) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.
Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHC Ⅱ can be raised in the barrier and then gradually mated in the conventional environment.
Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHC Ⅰ and Ⅱ deletion.
机标关键词：ggta1humanciitacmahgenespigs4galnt2compromises
论文发表日期：2024-08-28
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：7( 584-590 )
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