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Genetically modified pigs with α1,3-galactosyltransferase knockout and beyond: a comprehensive review of xenotransplantation strategies

cris.virtual.author-orcid0000-0002-2166-0556
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cris.virtual.author-orcid0000-0002-1208-3291
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cris.virtualsource.author-orciddcf5a6dd-b900-4dc0-abb1-88b0ce50b346
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cris.virtualsource.author-orcid0e52860c-9c5d-441c-b9ad-689938b2c236
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dc.abstract.enXenotransplantation holds promise to eliminate the shortage of organs intended for humans in need. Pigs constitute the most suitable organ xenograft donor due to the fact that their organ anatomy physiological metabolism and immune system resemble those of humans. However, swine organs rapidly cause hyperacute rejection (HAR) and acute humoral xenograft rejection (AHXR) after transplantation. HAR and AHXR are caused by the presence of xenoreactive natural immunoglobulins directed toward a galactose alpha1-3-galactose (alpha-Gal) epitope on porcine vascular endothelium. In order to suppress both types of rejection, pigs with alpha1,3-galactosyltransferase gene knockout (GT-KO) and other genetic modifications (like simultaneous expression of the human complementary regulatory proteins) are intensively investigated. This review highlights the usefulness of GT-KO pig – derived organs such as kidney, heart, corneal, and lung in xenotransplantation. To obtain transgenic pigs researchers can use several techniques based on pronuclear and cytoplasmic microinjection, somatic cell nuclear transfer (SCNT), viral transduction of DNA and DNA transposable element -based technology, site specific nucleases and modifications of the CRISPR/Cas bacterial immune system. Some additional strategies like targeted immunosuppression or tolerance induction of B and T cells will be essential for sustained survival of xenografts. Although xenotransplantation with the use of pigs is a very rapidly evolving field, more research is needed to create perfectly compatible with the human immune system organs.
dc.affiliationWydział Rolnictwa, Ogrodnictwa i Biotechnologii
dc.affiliation.instituteKatedra Biochemii i Biotechnologii
dc.contributor.authorStelcer, Ewelina
dc.contributor.authorWoźniak, Anna
dc.contributor.authorMagner, Dorota
dc.contributor.authorZeyland, Joanna
dc.date.access2025-11-04
dc.date.accessioned2025-11-04T09:54:55Z
dc.date.available2025-11-04T09:54:55Z
dc.date.copyright2025-11-04
dc.date.issued2025
dc.description.abstract<jats:p>Xenotransplantation holds promise to eliminate the shortage of organs intended for humans in need. Pigs constitute the most suitable organ xenograft donor due to the fact that their organ anatomy physiological metabolism and immune system resemble those of humans. However, swine organs rapidly cause hyperacute rejection (HAR) and acute humoral xenograft rejection (AHXR) after transplantation. HAR and AHXR are caused by the presence of xenoreactive natural immunoglobulins directed toward a galactose alpha1-3-galactose (alpha-Gal) epitope on porcine vascular endothelium. In order to suppress both types of rejection, pigs with alpha1,3-galactosyltransferase gene knockout (GT-KO) and other genetic modifications (like simultaneous expression of the human complementary regulatory proteins) are intensively investigated. This review highlights the usefulness of GT-KO pig – derived organs such as kidney, heart, corneal, and lung in xenotransplantation. To obtain transgenic pigs researchers can use several techniques based on pronuclear and cytoplasmic microinjection, somatic cell nuclear transfer (SCNT), viral transduction of DNA and DNA transposable element -based technology, site specific nucleases and modifications of the CRISPR/Cas bacterial immune system. Some additional strategies like targeted immunosuppression or tolerance induction of B and T cells will be essential for sustained survival of xenografts. Although xenotransplantation with the use of pigs is a very rapidly evolving field, more research is needed to create perfectly compatible with the human immune system organs.</jats:p>
dc.description.accesstimeat_publication
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.if5,9
dc.description.points140
dc.description.versionfinal_published
dc.description.volume16
dc.identifier.doi10.3389/fimmu.2025.1663246
dc.identifier.issn1664-3224
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/5709
dc.identifier.weblinkhttp://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1663246/full
dc.languageen
dc.relation.ispartofFrontiers in Immunology
dc.relation.pagesart. 1663246
dc.rightsCC-BY
dc.sciencecloudnosend
dc.share.typeOPEN_JOURNAL
dc.subject.enalpha-1
dc.subject.en3-galactosyltransferase
dc.subject.enalpa-Gal epitope
dc.subject.enxenotransplantation
dc.subject.enhyperacute rejection (HAR)
dc.subject.enanti-Gal specific antibodies
dc.titleGenetically modified pigs with α1,3-galactosyltransferase knockout and beyond: a comprehensive review of xenotransplantation strategies
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.volume16