The success of organ transplantation is limited by the complications of immunosuppression, by chronic rejection, and by the insufficient organ supply, and thousands of patients die every year while waiting for a transplant. With recent progress in xenotransplantation permitting porcine organ graft survival of months or even years in nonhuman primates, there is renewed interest in its potential to alleviate the organ shortage. Many of these advances are the result of our heightened capacity to modify pigs genetically, particularly with the development of CRISPR-Cas9–based gene editing methodologies. Although this approach allows the engineering of pig organs that are less prone to rejection, the clinical application of xenotransplantation will require the ability to avoid the ravages of a multifaceted attack on the immune system while preserving the capacity to protect both the recipient and the graft from infectious microorganisms. In this review, we will discuss the potential and limitations of these modifications and how the engineering of the graft can be leveraged to alter the host immune response so that all types of immune attack are avoided.

器官移植的成功受到免疫抑制并发症，慢性排斥反应和器官供应不足的限制，每年有数千名患者在等待移植过程中死亡。随着异种移植的最新进展允许猪器官移植物在非人类灵长类动物中存活数月甚至数年，人们对其减轻器官短缺的潜力有了新的兴趣。这些进步中的许多是我们提高基因改造猪的能力的结果，特别是随着基于CRISPR-Cas9的基因编辑方法的发展。尽管这种方法允许对不那么容易排斥的猪器官进行工程改造，异种移植的临床应用将需要能够避免对免疫系统多方面攻击的破坏，同时保留保护受体和移植物免受传染性微生物侵袭的能力。在这篇综述中，我们将讨论这些修饰的潜力和局限性，以及如何利用移植物的工程技术来改变宿主的免疫反应，从而避免所有类型的免疫攻击。