Animal Molecular Breeding 2024, Vol.14, No.1, 106-118 http://animalscipublisher.com/index.php/amb 112 4.2 Long-term studies on survival and functionality of genetically modified pig organs Long-term studies have shown promising results regarding the survival and functionality of genetically modified pig organs. Research has indicated that organs from pigs with multiple genetic modifications, such as the deletion of carbohydrate xenoantigens and the expression of human complement-regulatory proteins, can function for clinically valuable periods, exceeding 12 months in some cases (Cooper et al., 2019). Additionally, preclinical models have demonstrated prolonged xenograft survival times for various organs, including the heart, liver, kidney, and lung, in pig-to-non-human primate models (Lu et al., 2020). These findings suggest that genetically modified pig organs can maintain functionality and viability over extended periods, making them a viable option for clinical xenotransplantation. 4.3 Comparison of genetically modified organs versus non-modified controls Comparative studies between genetically modified and non-modified pig organs have consistently shown superior outcomes for the former. For instance, GBC-3KO pig skin grafts exhibited significantly prolonged survival compared to wild-type pig skin grafts in immunocompetent mice (Fu et al., 2020). Similarly, kidneys from genetically modified pigs transplanted into brain-dead human recipients showed improved renal function and no signs of hyperacute rejection, whereas non-modified controls would likely have faced immediate rejection (Montgomery et al., 2022). These comparisons underscore the critical role of genetic modifications in enhancing the compatibility and performance of pig organs for xenotransplantation. 5 Ethical and Regulatory Considerations 5.1 Ethical issues surrounding genetic modifications in animals The ethical implications of genetic modifications in animals, particularly pigs for xenotransplantation, are multifaceted and complex. One primary concern is the welfare of the genetically modified animals. These animals are often kept in laboratory conditions that may not meet their biological and psychological needs, raising significant animal welfare issues (Lei et al., 2022). The process of genetic modification itself, which includes techniques such as CRISPR/Cas9, can also be ethically contentious due to the potential for unforeseen consequences and the manipulation of animal genomes for human benefit (Kararoudi et al., 2018). Additionally, there are broader ethical debates about whether humans should engage in genetic engineering at all, with some arguing that it represents a form of technological overreach (Lei et al., 2022). 5.2 Regulatory frameworks governing xenotransplantation and genetic engineering The regulatory landscape for xenotransplantation and genetic engineering is evolving but remains stringent. National regulatory authorities require extensive evidence to justify each genetic modification in donor pigs, often based on in vitro and in vivo experimental data (Cooper et al., 2019). The International Society for Heart and Lung Transplantation, for example, has set specific benchmarks for graft survival in large animal models before clinical trials can proceed (Mohiuddin et al., 2019). Regulatory frameworks also address the potential risks of zoonotic diseases, necessitating rigorous infectious disease surveillance and the notification of close contacts of recipients (Johnson, 2022). These frameworks aim to balance the potential benefits of xenotransplantation with the need to ensure safety and ethical integrity. 5.3 Public perception and ethical debates Public perception of genetic modifications in animals and xenotransplantation is influenced by a variety of ethical and societal concerns. There is often a lack of understanding of the science behind these technologies, which can lead to spurious ethical concerns, such as the belief that xenotransplantation violates natural or religious principles (Rollin, 2020). Public debates also focus on the integrity and naturalness of animals, risk perception, and animal welfare issues (Eriksson et al., 2018). The ethical acceptability of using genetically modified animals for organ transplants is further complicated by concerns about justice and equity in organ distribution, as well as the potential exacerbation of existing healthcare inequities (Johnson, 2022). Engaging the public in informed discussions and addressing these ethical concerns transparently is crucial for the advancement of xenotransplantation technologies.
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