Evidence map›Paper›PMID 38962826›Full record

ArticleAnimal models and experimental medicine2024

Elimination of GGTA1, CMAH, β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions.

Jing Xu, Jilong Ren, Kai Xu, Minghui Fang, Meina Ka, Fei Xu, Xin Wang, Jing Wang, Zhiqiang Han, Guihai Feng and 4 more

Abstract read
In one paragraph

Article in Animal models and experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Jing XuState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Jilong RenState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Kai XuState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Minghui FangKey Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, Jilin University, Changchun, China.
Meina KaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Fei XuKey Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, Jilin University, Changchun, China.
Xin WangState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Jing WangState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zhiqiang HanState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Guihai FengState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Ying ZhangState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Tang HaiState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Wei LiState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zheng HuKey Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, Jilin University, Changchun, China.

Funding

CAS Project for Young Scientists in Basic Research YSBR-012National Key Research and Development Program 2019YFA0903800National Key Research and Development Program 2021YFA0805701National Key Research and Development Program 2021YFA0805905National Key Research and Development Program 2022YFA1103603National Natural Science Foundation of China 32071456National Natural Science Foundation of China 82241224STI 2030-Major Project 2023ZD0407503Strategic Priority Research Program of the Chinese Academy of Sciences XDA16030000
6 · The paper itself

Abstract

backgroundPig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies 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.

methodsThus, 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.

resultsWe 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.

conclusions4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.

Indexed as

Graft RejectionN-AcetylgalactosaminyltransferasesTransplantation, HeterologousAnimalsAnimals, Genetically ModifiedCRISPR-Cas SystemsGalactosyltransferasesGene EditingGene Knockout TechniquesHumansMixed Function OxygenasesNuclear ProteinsSwineTrans-Activatorsalpha-1,3-galactosyltransferase 1, porcinebeta-1,4-N-acetyl-galactosaminyl transferase 2CMPacetylneuraminate monooxygenaseGalactosyltransferasesMHC class II transactivator proteinMixed Function OxygenasesN-AcetylgalactosaminyltransferasesNuclear ProteinsTrans-ActivatorsCD4 T cellgenetically edited pigimmune rejectionmajor histocompatibility complex IIxenotransplantation

Identifiers

PMID38962826
PMCPMC11369026

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.