International Journal of Molecular Zoology 2024, Vol.14, No.4, 244-254 http://animalscipublisher.com/index.php/ijmz 252 9 Concluding Remarks The research on genetically engineered pigs for xenotransplantation has made significant strides in addressing the critical shortage of human donor organs. Key advancements include the development of pigs with inactivated porcine endogenous retroviruses (PERVs) and multiple genetic modifications to enhance immunological compatibility and reduce the risk of zoonotic infections. These modifications include the deletion of pig-specific antigens and the insertion of human complement and coagulation-regulatory transgenes, which have shown promising results in preclinical studies. Additionally, the establishment of designated pathogen-free (DPF) pig herds has been crucial in minimizing the risk of virus transmission during xenotransplantation. The progress in genetic engineering of pigs opens new avenues for clinical applications of xenotransplantation. Future research should focus on optimizing the genetic modifications to further reduce immunological barriers and enhance the longevity and functionality of xenografts in human recipients. Moreover, the development of more sophisticated screening and monitoring techniques for potential zoonotic pathogens, including single-stranded DNA viruses, is essential to ensure the safety of xenotransplantation procedures. Clinical trials are needed to validate the efficacy and safety of these genetically engineered pigs in human patients, which will require rigorous regulatory oversight and ethical considerations. Continued research is imperative to address the remaining challenges in xenotransplantation, including the refinement of genetic modifications and the prevention of cross-species virus transmission. Researchers and clinicians must collaborate to develop standardized protocols for the production and screening of pathogen-free pigs. Ethical considerations, such as the potential psychological impact on recipients and the broader societal implications of xenotransplantation, must be carefully evaluated and addressed. It is crucial to engage with regulatory bodies, ethicists, and the public to ensure that the benefits of xenotransplantation are realized in a responsible and ethically sound manner. In conclusion, while significant progress has been made in the field of xenotransplantation, ongoing research and ethical vigilance are essential to overcome the remaining hurdles and to bring this promising solution to clinical reality. Acknowledgments Author extends sincere thanks to two anonymous peer reviewers for their invaluable feedback on the initial draft of this manuscript. Conflict of Interest Disclosure Author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Ali A., Kemter E., and Wolf E., 2023, Advances in organ and tissue xenotransplantation, Annual Review of Animal Biosciences, 12(1): 369-390. https://doi.org/10.1146/annurev-animal-021122-102606 PMid:37906838 Cengiz N., and Wareham C., 2019, Pig-to-human xenotransplantation: overcoming ethical obstacles, South African Journal of Bioethics and Law, 12(2): 66-70. https://doi.org/10.7196/SAJBL.2019.v12i2.00677 Denner J., 2021, Porcine endogenous retroviruses and xenotransplantation, 2021, Viruses, 13(11): 2156. https://doi.org/10.3390/v13112156 PMid:34834962 PMCid:PMC8625113 Denner J., 2022, Virus safety of xenotransplantation, Viruses, 14(9): 1926. https://doi.org/10.3390/v14091926 PMid:36146732 PMCid:PMC9503113 Eisenson D., Hisadome Y., and Yamada K., 2022, Progress in xenotransplantation: immunologic barriers, advances in gene editing, and successful tolerance induction strategies in pig-to-primate transplantation, Frontiers in Immunology, 13: 899657. https://doi.org/10.3389/fimmu.2022.899657 PMid:35663933 PMCid:PMC9157571 Fishman J., 2018, Infectious disease risks in xenotransplantation, American Journal of Transplantation, 18(8): 1857-1864. https://doi.org/10.1111/ajt.14725 PMid:29513380
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