Gene-Edited Pig Organ Xenotransplantation: Translational Progress and Clinical Safety Challenges
DOI:
https://doi.org/10.66238/fsrma78Keywords:
Xenotransplantation, Gene Editing, Immunological Rejection, Clinical SafetyAbstract
The persistent and widening disparity between the demand for transplantable human organs and their availability has precipitated a global health crisis, driving the exploration of alternative therapeutic modalities. Xenotransplantation, specifically utilizing organs from genetically engineered porcine models, has recently transitioned from theoretical and preclinical paradigms to early-stage clinical reality. This transition has been fundamentally enabled by the advent of advanced genomic editing technologies, notably the clustered regularly interspaced short palindromic repeats associated protein 9 system, which allows for precise, multiplexed alterations of the porcine genome. These genetic modifications are designed to circumvent devastating hyperacute immunological rejection, mitigate coagulation dysregulation, and reduce the risk of zoonotic disease transmission, particularly concerning porcine endogenous retroviruses. This comprehensive paper examines the translational progress of gene-edited pig organ xenotransplantation, analyzing recent clinical milestones involving cardiac and renal grafts in human decedents and compassionate use patients. Furthermore, it deeply investigates the critical clinical safety challenges that persist, including the insidious threat of latent porcine pathogens such as porcine cytomegalovirus, the complex mechanisms of delayed graft rejection, and the intricate ethical and regulatory frameworks required to govern first-in-human clinical trials. By synthesizing current empirical data and theoretical models, this research highlights the transformative potential of xenotransplantation while underscoring the imperative for rigorous risk management and international regulatory consensus to ensure patient and public safety.
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