International Journal of Clinical Case Reports 2024, Vol.14, No.2, 94-106 http://medscipublisher.com/index.php/ijccr 103 Moreover, strategies to enhance organ longevity through genetic modifications have been developed, focusing on increasing resistance to ischemia-reperfusion injury, reducing inflammation, and promoting tissue repair. The utilization of CRISPR-Cas9 to upregulate anti-apoptotic and antioxidant pathways, such as Bcl-2 and Nrf2, has shown potential in improving the durability and function of transplanted organs. The findings underscore the transformative potential of CRISPR-Cas9 in xenotransplantation, paving the way for more refined and efficient genetic modifications to improve organ compatibility and longevity. Future research should focus on overcoming technical challenges, such as optimizing delivery methods and minimizing off-target effects, to enhance the precision and safety of gene editing. Additionally, long-term studies are essential to evaluate the stability and durability of the genetic modifications and their effects on organ function over time. The development of non-viral delivery systems and high-fidelity Cas9 variants will be crucial in addressing current limitations and advancing clinical applications. To fully realize the potential of CRISPR-Cas9 in xenotransplantation, continued interdisciplinary research and collaboration are vital. Researchers, clinicians, bioethicists, and regulatory bodies must work together to address the technical, ethical, and social challenges associated with gene editing. Ethical considerations, particularly concerning animal welfare and the potential for unintended consequences, must be integrated into the research framework to ensure responsible and sustainable advancements. Public engagement and transparency in the research process are also crucial to build trust and acceptance of gene-edited organs. Open dialogue about the benefits, risks, and ethical implications of CRISPR-Cas9 technology will help align scientific advancements with societal values and expectations. Acknowledgments We would like to express our gratitude to the two anonymous peer reviewers for their critical assessment and constructive suggestions on our manuscript. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Akçakaya P., Bobbin M.L., Guo J.A., Malagón-López J., Clement K., Garcia S., and Joung J., 2018, In vivo CRISPR editing with no detectable genome-wide off-target mutations, Nature, 561(7723): 416-419. https://doi.org/10.1038/s41586-018-0500-9 Ali A., Kemter E., and Wolf E., 2023, Advances in Organ and Tissue Xenotransplantation, Annual Review of Animal Biosciences, 12: 369-390. https://doi.org/10.1146/annurev-animal-021122-102606 Ayanoğlu F., Elçin A.E., and Elçin Y.M., 2020, Bioethical issues in genome editing by CRISPR-Cas9 technology, Turkish Journal of Biology, 44: 110-120. https://doi.org/10.3906/biy-1912-52 Bilbao G., Contreras J., Eckhoff D., Mikheeva G.V., Krasnykh V., Douglas J.T., and Curiel D., 1999, Reduction of ischemia-reperfusion injury of the liver by in vivo adenovirus-mediated gene transfer of the antiapoptotic Bcl-2 gene, Annals of Surgery, 230(2): 185-193. https://doi.org/10.1097/00000658-199908000-00008 Bonaccorsi-Riani E., Gillooly A.R., Iesari S., Brüggenwirth I., Ferguson C.M., Komuta M., and Martins P.N., 2022, Delivering siRNA Compounds During HOPE to Modulate Organ Function: A Proof-of-concept Study in a Rat Liver Transplant Model, Transplantation, 106(10): 1565-1576. https://doi.org/10.1097/TP.0000000000004175 Cao J., Wu L., Zhang S.M., Lu M., Cheung W.C., Cai W.L., and Yan Q., 2016, An easy and efficient inducible CRISPR/Cas9 platform with improved specificity for multiple gene targeting, Nucleic Acids Research, 44, e149. https://doi.org/10.1093/nar/gkw660 Collins P.J., Hale C., and Xu H., 2017, Edited course of biomedical research: leaping forward with CRISPR, Pharmacological Research, 125: 258-265. https://doi.org/10.1016/j.phrs.2017.09.008
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==