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<p>Xenotransplantation, the transplantation of organs, tissues or cells across species, offers a potential solution to the shortage of human organs for patients with organ failure. Porcine organs, which share key physiological, anatomical and immunological features with human organs, are currently the primary focus of preclinical and clinical xenotransplantation studies. In this Review, we examine major considerations and barriers in xenotransplantation, including species selection, hyperacute and acute rejection, and xenozoonosis, and discuss strategies to overcome these challenges through gene editing and immunomodulation. We emphasize the need to address antibody-mediated rejection, control complement activation, block co-stimulatory pathways, optimize graft preservation, develop high-fidelity endothelial models, identify additional porcine antigens, and promote immunohomeostasis and tissue repair. Furthermore, robust safety protocols, surveillance systems and mechanisms for ethical transparency are essential. The future success of xenotransplantation will depend on innovative technologies and refined models to resolve these complex challenges.</p>

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Overcoming xenotransplantation barriers through gene editing and immunomodulation

  • 期刊论文

  • 发表日期：

    2026年2月23日

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  • Andy Tully,
  • Avneesh K. Singh,
  • Javier Galindo,
  • Bartley P. Griffith,
  • Muhammad M. Mohiuddin

摘要

Xenotransplantation, the transplantation of organs, tissues or cells across species, offers a potential solution to the shortage of human organs for patients with organ failure. Porcine organs, which share key physiological, anatomical and immunological features with human organs, are currently the primary focus of preclinical and clinical xenotransplantation studies. In this Review, we examine major considerations and barriers in xenotransplantation, including species selection, hyperacute and acute rejection, and xenozoonosis, and discuss strategies to overcome these challenges through gene editing and immunomodulation. We emphasize the need to address antibody-mediated rejection, control complement activation, block co-stimulatory pathways, optimize graft preservation, develop high-fidelity endothelial models, identify additional porcine antigens, and promote immunohomeostasis and tissue repair. Furthermore, robust safety protocols, surveillance systems and mechanisms for ethical transparency are essential. The future success of xenotransplantation will depend on innovative technologies and refined models to resolve these complex challenges.