中国猪业2025,Vol.20Issue(2):4-14,11.DOI:10.16174/j.issn.1673-4645.2025.03.001
基因编辑异种器官移植供体猪的研究进展
Research Progress in Gene Editing Xenotransplantation Donor Pigs
摘要
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 theβ2M 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 liv-ers 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.关键词
猪/基因编辑/异种器官移植/CRISPR/Cas9/动物模型Key words
pig/gene editing/xenotransplantation/CRISPR/Cas9/animal model分类
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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):4-14,11.基金项目
国家重点研发计划项目(2021YFA0805905) (2021YFA0805905)