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Trio deep-sequencing does not reveal unexpected mutations in Cas9-edited monkeys

Xin Luo, Yaoxi He, Chao Zhang, Xiechao He, Lanzhen Yan, Min Li, Ting Hu, Yan Hu, Jin Jiang, Xiaoyu Meng, Weizhi Ji, Xudong Zhao, Ping Zheng, Shuhua Xu, Bing Su
doi: https://doi.org/10.1101/339143
Xin Luo
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Yaoxi He
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Chao Zhang
2Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, CAS, Shanghai, 200031, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Xiechao He
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
7Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223, China
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Lanzhen Yan
3Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650203, China
7Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223, China
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Min Li
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Ting Hu
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Yan Hu
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Jin Jiang
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Xiaoyu Meng
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5University of Chinese Academy of Sciences, Beijing 100101, China
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Weizhi Ji
6Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China
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Xudong Zhao
3Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650203, China
7Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223, China
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Ping Zheng
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
4Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
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  • For correspondence: sub@mail.kiz.ac.cn xushua@picb.ac.cn zhengp@mail.kiz.ac.cn
Shuhua Xu
2Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, CAS, Shanghai, 200031, China
4Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
8School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
9Collaborative Innovation Centre of Genetics and Development, Shanghai 200438, China
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  • For correspondence: sub@mail.kiz.ac.cn xushua@picb.ac.cn zhengp@mail.kiz.ac.cn
Bing Su
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
4Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
6Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China
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  • For correspondence: sub@mail.kiz.ac.cn xushua@picb.ac.cn zhengp@mail.kiz.ac.cn
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Abstract

CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect remains a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, no comprehensive in vivo off-target assessment has been conducted in NHPs. Here we performed whole genome trio sequencing of Cas9-treated monkeys. We found they only carried a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected mutations were detected.

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Posted June 05, 2018.
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Trio deep-sequencing does not reveal unexpected mutations in Cas9-edited monkeys
Xin Luo, Yaoxi He, Chao Zhang, Xiechao He, Lanzhen Yan, Min Li, Ting Hu, Yan Hu, Jin Jiang, Xiaoyu Meng, Weizhi Ji, Xudong Zhao, Ping Zheng, Shuhua Xu, Bing Su
bioRxiv 339143; doi: https://doi.org/10.1101/339143
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Trio deep-sequencing does not reveal unexpected mutations in Cas9-edited monkeys
Xin Luo, Yaoxi He, Chao Zhang, Xiechao He, Lanzhen Yan, Min Li, Ting Hu, Yan Hu, Jin Jiang, Xiaoyu Meng, Weizhi Ji, Xudong Zhao, Ping Zheng, Shuhua Xu, Bing Su
bioRxiv 339143; doi: https://doi.org/10.1101/339143

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