Journal of Vaccine Research 2024, Vol.14, No.3, 120-134 http://medscipublisher.com/index.php/jvr 120 Research Report Open Access Regulatory Mechanisms of Graft Longevity: Insights from Genetically Modified Pig Organs YunLiu The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 311202, Zhejiang, China Corresponding email: liuyun@hotmail.com Journal of Vaccine Research, 2024, Vol.14, No.3 doi: 10.5376/jvr.2024.14.0013 Received: 21 Apr., 2024 Accepted: 25 May, 2024 Published: 06 Jun., 2024 Copyright © 2024 Liu, 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: Liu Y., 2024, Regulatory mechanisms of graft longevity: insights from genetically modified pig organs, Journal of Vaccine Research, 14(3): 120-134 (doi: 10.5376/jvr.2024.14.0013) Abstract This study focuses on exploring the regulatory mechanisms that enhance graft longevity through genetically modified pig organs. The discussion centers on genetic modifications designed to improve immune compatibility and graft survival. Key gene editing technologies, such as CRISPR/Cas9, have enabled precise modifications of the pig genome, reducing immunogenicity and improving physiological compatibility. Experimental studies have shown the effectiveness of these modifications in preventing organ rejection and enhancing organ function in non-human primates and preliminary human trials. This study also addresses ethical considerations, including animal welfare and long-term genetic stability, as well as the regulatory frameworks governing xenotransplantation. It emphasizes the importance of interdisciplinary research, the development of immune tolerance strategies, and the integration of bioengineering approaches. This study highlights the potential of genetically modified pig organs as a viable solution to the organ shortage crisis, paving the way for future clinical applications. Keywords Xenotransplantation; Genetic Modification; Graft Longevity; Immune Compatibility; CRISPR/Cas9 1 Introduction Organ transplantation has become an effective treatment for patients with end-stage organ failure. However, the shortage of donor organs results in many patients losing their lives while waiting for a suitable match. To address this challenge, scientists have explored xenotransplantation, specifically using animal organs to replace human ones, with pigs being a focal point due to the similarity of their organs to humans. Despite the challenges of immune rejection, gene-editing technologies like CRISPR/Cas9 have shown potential in modifying pig genetics to reduce immunogenicity and increase survival rates (Lei et al., 2022). The success of xenotransplantation hinges on overcoming immune rejection. While traditional immunosuppressive therapies offer some relief, they come with significant side effects. Researchers have managed to knock out the GGTA1 gene in pigs, effectively reducing the expression of α-Gal antigens and lowering the risk of hyperacute rejection. Additionally, the introduction of human complement regulatory proteins such as CD55 and CD59 has significantly inhibited the activation of the complement system, reducing acute rejection (Cooper et al., 2019). Beyond immune rejection, this research also focuses on the long-term survival and functional maintenance of transplants. Genetic modifications have enhanced the transplant's resistance to ischemia-reperfusion injury and used immunoregulatory genes to mitigate chronic inflammatory responses. Scientists are also studying how to balance the functionality of the transplant with the immunosuppressive treatment needs of patients, ensuring the stability and safety of genetic modifications (Sykes and Sachs, 2019). This study reviews the main research progress and challenges in transgenic pig organ transplantation, exploring the molecular mechanisms that regulate the lifespan of transplants. It aims to provide a theoretical basis and reference for future xenotransplantation research and clinical applications. By deeply analyzing the roles of genetic modification and immune regulation, this study not only advances the scientific field but also offers new approaches and technological paths to address the global organ shortage. Additionally, the discussion on ethical and regulatory issues lays the groundwork for the safety and efficacy of this emerging technology.
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