Human immune reactivity of GGTA1/CMAH/A3GALT2 triple knockout Yucatan miniature pigs

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dc.contributor.authorJ Shin-
dc.contributor.authorN Ko-
dc.contributor.authorH J Kim-
dc.contributor.authorY Lee-
dc.contributor.authorJeong Woong Lee-
dc.contributor.authorD I Jin-
dc.contributor.authorH Kim-
dc.contributor.authorK Choi-
dc.date.accessioned2021-09-30T15:30:19Z-
dc.date.available2021-09-30T15:30:19Z-
dc.date.issued2021-
dc.identifier.issn09628819-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/24812-
dc.description.abstractIn this study, we investigated the effect of a triple knockout of the genes alpha-1,3-galactosyltransferase (GGTA1), cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH), and alpha 1,3-galactosyltransferase 2 (A3GALT2) in Yucatan miniature pigs on human immune reactivity. We used the CRISPR/Cas9 system to create pigs lacking GGTA1 (GTKO) and GGTA1/CMAH/A3GALT2 triple gene knockout (TKO). The expression of all three xenoantigens was absent in TKO pigs, but there was no additional reduction in the level of Galα1,3Gal (αGal) epitopes expression in the A3GALT2 gene KO. Peripheral blood mononuclear cells (PBMCs), aorta endothelial cells (AECs), and cornea endothelial cells (CECs) were isolated from these pigs, and their ability to bind human IgM/IgG and their cytotoxicity in human sera were evaluated. Compared to wild type (WT) pigs, the level of human antibody binding of the PBMCs, AECs, and CECs of the transgenic pigs (GTKO and TKO) was significantly reduced. However, there were significant differences in human antibody binding between GTKO and TKO depending on the cell type. Human antibody binding of TKO pigs was less than that of GTKO on PBMCs but was similar between GTKO and TKO pigs for AECs and CECs. Cytotoxicity of transgenic pig (GTKO and TKO) PBMCs and AECs was significantly reduced compared to that of WT pigs. However, TKO pigs showed a reduction in cytotoxicity compared to GTKO pigs on PBMCs, whereas in AECs from both TKO and GTKO pigs, there was no difference. The cytotoxicity of transgenic pig CECs was significantly decreased from that of WT at 300 min, but there was no significant reduction in TKO pigs from GTKO. Our results indicate that genetic modification of donor pigs for xenotransplantation should be tailored to the target organ and silencing of additional genes such as CMAH or A3GALT2 based on GTKO might not be essential in Yucatan miniature pigs.-
dc.publisherSpringer-
dc.titleHuman immune reactivity of GGTA1/CMAH/A3GALT2 triple knockout Yucatan miniature pigs-
dc.title.alternativeHuman immune reactivity of GGTA1/CMAH/A3GALT2 triple knockout Yucatan miniature pigs-
dc.typeArticle-
dc.citation.titleTransgenic Research-
dc.citation.number5-
dc.citation.endPage634-
dc.citation.startPage619-
dc.citation.volume30-
dc.contributor.affiliatedAuthorJeong Woong Lee-
dc.contributor.alternativeName심주현-
dc.contributor.alternativeName고나영-
dc.contributor.alternativeName김형주-
dc.contributor.alternativeName이용진-
dc.contributor.alternativeName이정웅-
dc.contributor.alternativeName진동일-
dc.contributor.alternativeName김현일-
dc.contributor.alternativeName최기명-
dc.identifier.bibliographicCitationTransgenic Research, vol. 30, no. 5, pp. 619-634-
dc.identifier.doi10.1007/s11248-021-00271-w-
dc.subject.keywordCRISPR/Cas9-
dc.subject.keywordGGTA1-
dc.subject.keywordCMAH-
dc.subject.keywordA3GALT2-
dc.subject.keywordAntibody binding-
dc.subject.keywordCytotoxicity-
dc.subject.localCRISPR/Cas9-
dc.subject.localCytotoxicity-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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