International Journal of Clinical Case Reports 2024, Vol.14, No.2, 94-106 http://medscipublisher.com/index.php/ijccr 94 Feature Review Open Access Gene Editing for Organ Transplants: Evaluating the Impact of CRISPR/Cas9 on Immunogenicity and Organ Longevity in Pigs Junhui Li 1 , JiongLi 2 1 Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, Zhejiang, China 2 Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: jianhuili@jicat.org International Journal of Clinical Case Reports 2024, Vol.14, No.2 doi: 10.5376/ijccr.2024.14.0012 Received: 10 Apr., 2024 Accepted: 13 May, 2024 Published: 25 May., 2024 Copyright © 2024 Li and Li, 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: Li J.H., and Li J., 2024, Gene editing for organ transplants: evaluating the impact of CRISPR/Cas9 on immunogenicity and organ longevity in pigs, International Journal of Clinical Case Reports, 14(2): 94-106 (doi: 10.5376/ijccr.2024.14.0012) Abstract This study explores the application of CRISPR-Cas9 gene editing technology in organ transplantation, particularly its potential in reducing immunogenicity and enhancing the longevity of pig organs. The research focuses on strategies to reduce immune rejection through gene editing, specifically targeting genes such as GGTA1, CMAH, and β4GalNT2. Experimental results demonstrate that these genetic modifications significantly reduce the immunogenicity of pig organs. The study also investigates mechanisms to improve organ tolerance and function through gene editing, such as upregulation of anti-apoptotic and antioxidant genes, and strategies to mitigate ischemia-reperfusion injury. The study concludes with an assessment of the potential breakthroughs and future prospects of CRISPR-Cas9 in xenotransplantation, emphasizing the technical challenges and ethical considerations that need to be addressed in future research and clinical applications. Keywords CRISPR-Cas9; Gene editing; Immunogenicity; Xenotransplantation Organ transplantation remains the definitive treatment for end-stage organ failure, significantly enhancing both the quality and longevity of life for patients with terminal heart, lung, liver, and kidney diseases. Despite advancements, the availability of suitable donor organs falls critically short of demand. This shortage results in high mortality rates among patients on transplant waiting lists, with over 10-15% of heart and liver transplant candidates dying each year while awaiting a compatible donor (Cravedi, 2019). This gap between supply and demand has prompted the exploration of alternative sources of organs, including xenotransplantation, which involves the transplantation of animal organs into humans. Pigs are particularly promising donors due to their physiological and anatomical similarities to humans, as well as their potential for genetic modification to reduce immunological barriers (Ekser et al., 2015). Gene editing, especially with the advent of CRISPR-Cas9 technology, has revolutionized the field of genetic engineering. CRISPR-Cas9 allows for precise modifications of the genome by targeting specific DNA sequences and introducing changes such as deletions, insertions, or replacements. This technology has been instrumental in creating genetically modified pigs that are better suited for xenotransplantation. For example, CRISPR-Cas9 has been used to inactivate porcine endogenous retroviruses (PERVs), which are integrated into the pig genome and pose a risk of cross-species viral transmission during xenotransplantation (Niu et al., 2017). These advancements have significantly improved the safety and viability of using pig organs for human transplants. The primary objective of this research is to evaluate the impact of CRISPR-Cas9-mediated gene editing on the immunogenicity and longevity of pig organs used in xenotransplantation. Immunogenicity refers to the ability of the transplanted organ to elicit an immune response in the human recipient, which can lead to rejection of the organ. By using CRISPR-Cas9 to modify specific genes, it is possible to reduce or eliminate these immune responses, thereby increasing the success rates of xenotransplantation. Additionally, understanding how these genetic modifications affect organ longevity is crucial for ensuring that the transplanted organs function effectively over long periods. This research holds significant potential to address the critical shortage of human
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