Animal Molecular Breeding 2024, Vol.14, No.1, 106-118 http://animalscipublisher.com/index.php/amb 106 Research Review Open Access Engineering Immune-Compatible Organs: Genetic Modifications in Pigs for Reduced Rejection in Human Recipients Xiaofang Lin Tropical Animal Medicine Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572024, Hainan, China Corresponding author: xiao'fanglin@hitar.org Animal Molecular Breeding, 2024, Vol.14, No.1 doi: 10.5376/amb.2024.14.0013 Received: 07 Jan., 2024 Accepted: 17 Feb., 2024 Published: 27 Feb., 2024 Copyright © 2024 Lin, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Lin X.F., 2024, Engineering immune-compatible organs: genetic modifications in pigs for reduced rejection in human recipients, Animal Molecular Breeding, 14(1): 106-118 (doi: 10.5376/amb.2024.14.0013) Abstract The shortage of human organs for transplantation has driven significant advancements in xenotransplantation, particularly using genetically modified pigs. This study examines the genetic modifications in pigs aimed at reducing immune rejection in human recipients. Recent studies have demonstrated the potential of porcine organs with multiple genetic modifications to overcome hyperacute rejection and improve graft survival. Key genetic alterations include the knockout of xenoantigens such as alpha-1,3-galactosyltransferase and the insertion of human complement and coagulation regulatory genes. These modifications have shown promising results in preclinical and early clinical trials, with some xenografts maintaining function without signs of rejection for extended periods. The study highlights the importance of continued research to optimize genetic modifications and address remaining immunological and physiological barriers to clinical xenotransplantation. Keywords Porcine organs; Xenotransplantation; Genetic modification; Immune rejection; CRISPR-Cas9 Organ transplantation has long been recognized as a life-saving treatment for patients with end-stage organ failure. However, the demand for human organs far exceeds the supply, leading to a significant shortage that results in the deaths of thousands of patients annually while they await transplants (Sykes and Sachs, 2019; Lu et al., 2020). This critical imbalance has driven the exploration of alternative sources of organs, including xenotransplantation, which involves the transplantation of organs from one species to another (Yue et al., 2020; Lei et al., 2022). Xenotransplantation, particularly using pigs as organ donors, has emerged as a promising solution to the organ shortage crisis. Pigs are considered suitable donors due to their physiological similarities to humans and their ability to be genetically modified to reduce immunological incompatibilities (Cooper et al., 2019; Xi et al., 2023). Recent advancements in genetic engineering, such as CRISPR-Cas9, have enabled the creation of pigs with multiple genetic modifications aimed at overcoming the major barriers to xenotransplantation, including hyperacute rejection and other immune responses (Sykes and Sachs, 2019; Yue et al., 2020). These modifications include the deletion of pig-specific antigens and the expression of human complement and coagulation regulatory proteins (Cooper et al., 2019; Wu et al., 2023). The primary objective of this study is to examine the various genetic modifications in pigs that have been developed to reduce the risk of organ rejection in human recipients. By systematically analyzing the current state of research, this study aims to highlight the most effective genetic strategies that have been employed to enhance the compatibility of pig organs with the human immune system. Understanding these genetic modifications is crucial for advancing the field of xenotransplantation and moving closer to clinical applications that could alleviate the organ shortage crisis. This review will also discuss the potential challenges and future directions in the genetic engineering of pigs for xenotransplantation, providing a comprehensive overview of the progress and prospects in this innovative field. By addressing these objectives, this study seeks to contribute to the ongoing efforts to develop viable and immune-compatible pig organs for human transplantation, ultimately improving patient outcomes and saving lives.
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