基因编辑异种器官移植供体猪的研究进展

doi:10.16174/j.issn.1673-4645.2025.02.001

摘要/Abstract

摘要： 摘要：异种器官移植作为解决全球器官短缺问题的潜在方案备受瞩目，其中基因编辑猪作为供体来源更是受到广泛关注。与传统器官移植面临诸多难题的情况相比，猪器官移植至人体时，主要会遭遇免疫排斥反应、凝血功能失调以及器官尺寸不匹配等问题。而CRISPR/Cas9等基因编辑技术，能够精准定位猪体内相关基因位点，实现对免疫原性抗原敲除（如敲除GGTA1基因）、补体激活抑制（如抑制β2M基因）、凝血功能调节（如调节vWF基因）以及器官生长控制（如控制GHR基因）等方面的定向改良，针对性地解决猪器官移植面临的问题。此外，引入人类转基因（如hCD47基因），还能进一步增强猪器官的免疫耐受性。目前，在全球范围内，已经成功开展了多例基因编辑猪肾、肝移植至人体的亚临床和临床研究，取得了显著的进展。不过，由于基因编辑工具的种类多样，其作用机制和安全性也存在差异，有一定的技术和安全门槛。因此，本文系统梳理了当前已进入亚临床和临床试验的异种器官移植供体猪所需编辑的关键基因以及具体的编辑手段，探讨与分析基因编辑工具的安全性和效率问题以及当前面临的机遇与挑战。在确保基因编辑安全有效的前提下，为优化相关基因编辑方法和推动后续研究提供一定的参考，以促进异种器官移植技术迈向新的台阶。

关键词: 猪, 基因编辑, 异种器官移植, CRISPR/Cas9, 动物模型

Abstract: Xenotransplantation had attracted much attention as a potential solution to the global organ shortage problem, with gene-edited pigs receiving even more attention as a source of donors. In contrasted to the numerous challenges faced in traditional or gan transplantation, when porcine organs were transplanted into humans, they primarily encounter issued such as immune rejection, coagulation dysfunction, and organ size mismatch. Gene-editing technologies like CRISPR/Cas9 could precisely target relevant gene loci in pigs, enabling targeted improvements in aspects such as the knockout of immunogenic antigens (e.g., knockout of the GGTA1 gene), inhibition of complement activation (e.g., inhibition of the β2M gene), regulation of coagulation function (e.g., regulation of the vWF gene), and control of organ growth (e.g., control of the GHR gene), thereby specifically addressing the problems associated with porcine organ transplantation. Additionally, the introduction of human transgenes(e.g., the hCD47 gene) could further enhance the immune toler ance of porcine organs. Globally, multiple subclinical and clinical studied on the transplantation of genetically edited pig kidneys and livers into humans had been successfully conducted, yielding remarkable progress. However, due to the wide variety of gene-editing tools, there were differences in their mechanisms of action and safety, presenting certain technical and safety thresholds. Therefore, this paper systematically summarized the key genes that need to be edited in donor pigs for xenotransplantation that had entered subclinical and clinical trials and the specific editing methods. It also explored and analyzed the safety and efficiency issues of gene-editing tools, as well as the current opportunities and challenges. On the premise of ensuring the safety and effectiveness of gene editing, this paper aimed to provide some references for optimizing relevant gene-editing methods and promoting subsequent research, so as to advance xenotransplantation technology to a new level.

Key words: pig, gene editing, xenotransplantation, CRISPR/Cas9, animal model

中图分类号: S828；S814.8

冯沈泂, 倪征钰, 马昭, 孙尉峻, 张林林, 杜旭光. 基因编辑异种器官移植供体猪的研究进展[J]. 中国猪业, 2025, 20(2): 5-14.

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