REVIEW article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1663246
Genetically modified pigs with α1,3-galactosyltransferase knockout and beyond: a comprehensive review of xenotransplantation strategies
Provisionally accepted
- Department of Biochemistry and Biotechnology, Faculty of Agronomy and Bioengineerring, Poznan University of Life Sciences, Poznan, Poland
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Xenotransplantation holds promise to eliminate the shortage of organs intended for humans in need. Pigs are consideredconstitute the most suitable organ xenograft donor due to the fact that their organ size anatomy physiological metabolism and immune system resemble those of human beingshumans. However, swine organs rapidly cause hyperacute rejection (HAR) and acute humoral xenograft rejection (AHXR) after transplantation. HAR and AHXR are triggered caused by the presence of xenoreactive natural antibodies immunoglobulins directed against 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 transposon-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 long-termsustained survival ofr 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.
Keywords: alpha-1,3-galactosyltransferase, alpha-gal epitope, xenotransplantation, Hyperacute rejection (HAR), anti-Gal specific antibodies
Received: 10 Jul 2025; Accepted: 21 Oct 2025.
Copyright: © 2025 Stelcer, Wozniak, Magner and Zeyland. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ewelina Stelcer, ewelina.stelcer@up.poznan.pl
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