International Journal of Molecular Zoology 2024, Vol.14, No.4, 244-254 http://animalscipublisher.com/index.php/ijmz 250 immune rejection in vitro (Yue et al., 2020). In another study, the transplantation of pig hearts into baboons, with the elimination of PCMV, resulted in significantly improved survival times, highlighting the importance of pathogen elimination in successful xenotransplantation (Denner, 2022). These case studies underscore the potential of genetically modified, pathogen-free pigs as viable organ donors for human transplantation, offering a promising solution to the organ shortage crisis (Wolf et al., 2019; Niu et al., 2020). By addressing both immunogenicity and organ compatibility through advanced genetic engineering techniques, the field of xenotransplantation is making significant strides towards safer and more effective clinical applications. 6 Ethical and Regulatory Considerations 6.1 Ethical issues in the genetic engineering of animals The genetic engineering of pigs for xenotransplantation raises several ethical concerns. One primary issue is the welfare of the genetically modified animals. The process of genetic modification and the subsequent use of these animals for organ harvesting can lead to significant suffering and raises questions about the moral status of these animals (Kemter et al., 2020). Additionally, there are concerns about the long-term ecological impacts of releasing genetically modified organisms into the environment, even if unintentionally (Wolf et al., 2019). The potential for creating interspecies chimeras, which involves combining human and animal cells, further complicates the ethical landscape, as it challenges traditional boundaries between species and raises questions about the nature of human identity and dignity (Xi et al., 2023). 6.2 Regulatory frameworks for approving genetically engineered pigs for xenotransplantation The regulatory landscape for genetically engineered pigs intended for xenotransplantation is complex and varies significantly across different jurisdictions. In the United States, the Food and Drug Administration (FDA) oversees the regulation of genetically modified animals under the New Animal Drug Application (NADA) process, which requires extensive safety and efficacy data before approval (Denner, 2022). The European Medicines Agency (EMA) has similar stringent requirements, focusing on the safety of both the recipient and the broader public health implications (Sykes and Sachs, 2019). These regulatory frameworks are designed to ensure that genetically engineered pigs do not pose undue risks, particularly concerning the transmission of zoonotic diseases and the long-term health of transplant recipients. 6.3 Public perception and acceptance of genetically modified pigs Public perception and acceptance of genetically modified pigs for xenotransplantation are critical factors that can influence the success of this technology. Public concerns often revolve around the safety and ethical implications of using genetically modified organisms. There is a significant need for transparent communication and public engagement to address these concerns and build trust. Studies have shown that public acceptance can be influenced by the perceived benefits of the technology, such as alleviating the organ shortage crisis, and by assurances regarding the safety and ethical treatment of the animals involved (Kemter et al., 2020; Lei et al., 2022). Effective regulatory oversight and clear ethical guidelines can also play a crucial role in shaping public opinion and acceptance (Sykes and Sachs, 2019; Denner, 2022). 7 Challenges and Limitations 7.1 Technical challenges in achieving complete pathogen elimination Achieving complete pathogen elimination in genetically engineered pigs for xenotransplantation is a significant technical challenge. Despite the establishment of Designated Pathogen-Free (DPF) facilities and rigorous screening methods, the risk of pathogen transmission remains. For instance, porcine endogenous retroviruses (PERVs) are integrated into the pig genome and cannot be eliminated by conventional methods, posing a potential risk for zoonotic transmission (Denner, 2022). Additionally, environmental factors and human activities can lead to outbreaks of pathogens such as porcine circovirus (PCV), even in controlled settings (Noordergraaf et al., 2018). Advanced genome editing techniques like CRISPR-Cas9 have been employed to inactivate PERVs, but the complete elimination of all potential pathogens remains a complex and ongoing challenge (Yue et al., 2020).
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