Genome-wide Genetic Mutations Accumulated in Pigs Genome-edited for Xenotransplantation and Their Filial Generation

Although xenotransplantation has been revolutionized by the development of genome-edited pigs, it is still unknown whether these pigs and their offspring remain genomically stable. Here, we showed that GGTA1-knockout (GTKO) pigs accumulated an average of 1205 genome-wide genetic mutations, and their filial 1 (F1) offspring contained an average of 18 de novo mutations compared with wild-type controls and their parents. The majority of mutations were in regions annotated as intergenic without altering protein functions, and none were located at predicted off-target sites. RNA sequencing analysis and phenotypic observations indicated that the accumulated mutations may have only a limited influence on GTKO pigs, and most of the mutations in the GTKO pigs could be attributed to the electrotransfection of plasmids into cells. This is the first report demonstrating that genetic mutations in genome-edited pigs are inherited stably by the next generation, providing a reference for the safe application and a standard approach to breed genome-edited pigs for xenotransplantation.

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Publication Details

Journal
Genomics Proteomics & Bioinformatics
Published
2025-08-20
DOI
https://doi.org/10.1093/gpbjnl/qzaf071
Citations
1
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
0.81

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article

Genome-wide Genetic Mutations Accumulated in Pigs Genome-edited for Xenotransplantation and Their Filial Generation

Shunmin He, Xiaoyan Du, Dengke Pan, Lixue Cao et al.
1 citations
Genomics Proteomics & Bioinformatics
CRISPR and Genetic Engineering
0.81
article

Genome-wide Genetic Mutations Accumulated in Pigs Genome-edited for Xenotransplantation and Their Filial Generation

Shunmin He, Xiaoyan Du, Dengke Pan, Lixue Cao, Chen Zhang, Jianyi Lv, Xiangyang Xing, Xianhui Sun, Yi-Biao Jiang, Xueyun Huo, Zhenwen Chen, Jingjing Zhang, Changlong Li, Meng Guo, Jing Lu, Xiao Zhu, Xin Liu
article en
1 citations

Abstract

Although xenotransplantation has been revolutionized by the development of genome-edited pigs, it is still unknown whether these pigs and their offspring remain genomically stable. Here, we showed that GGTA1-knockout (GTKO) pigs accumulated an average of 1205 genome-wide genetic mutations, and their filial 1 (F1) offspring contained an average of 18 de novo mutations compared with wild-type controls and their parents. The majority of mutations were in regions annotated as intergenic without altering protein functions, and none were located at predicted off-target sites. RNA sequencing analysis and phenotypic observations indicated that the accumulated mutations may have only a limited influence on GTKO pigs, and most of the mutations in the GTKO pigs could be attributed to the electrotransfection of plasmids into cells. This is the first report demonstrating that genetic mutations in genome-edited pigs are inherited stably by the next generation, providing a reference for the safe application and a standard approach to breed genome-edited pigs for xenotransplantation.

Genomics Proteomics & BioinformaticsVol. 23(4)
University of Electronic Science and Technology of China (CN), Capital Medical University (CN), Chinese Academy of Sciences (CN), Peking University (CN), Chengdu Medical College (CN), Czech Academy of Sciences, Institute of Biophysics (CZ), Peking University Cancer Hospital (CN), Chengdu Organic Chemicals (China) (CN), Institute of Biophysics (CN), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN), University of Chinese Academy of Sciences (CN)
National Natural Science Foundation of China
Openalex Percentile: Top 24%
CRISPR and Genetic Engineering
0.81
DOIOpen Access PDFOpenAlex
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