Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver
Abstract Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ...
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Nature Publishing Group
2021
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oai:doaj.org-article:3966e94a00e04700bdb552809b5edfc52021-12-05T12:07:19ZGeneration of in situ CRISPR-mediated primary and metastatic cancer from monkey liver10.1038/s41392-021-00799-72059-3635https://doaj.org/article/3966e94a00e04700bdb552809b5edfc52021-12-01T00:00:00Zhttps://doi.org/10.1038/s41392-021-00799-7https://doaj.org/toc/2059-3635Abstract Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.Liping ZhongYong HuangJian HeNuo YangBanghao XuYun MaJunjie LiuChao TangChengpiao LuoPan WuZongqiang LaiYu HuoTao LuDongni HuangWenlin GongLu GanYiqun LuoZhikun ZhangXiyu LiuYongxiang ZhaoNature Publishing GrouparticleMedicineRBiology (General)QH301-705.5ENSignal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-13 (2021) |
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DOAJ |
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| topic |
Medicine R Biology (General) QH301-705.5 |
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Medicine R Biology (General) QH301-705.5 Liping Zhong Yong Huang Jian He Nuo Yang Banghao Xu Yun Ma Junjie Liu Chao Tang Chengpiao Luo Pan Wu Zongqiang Lai Yu Huo Tao Lu Dongni Huang Wenlin Gong Lu Gan Yiqun Luo Zhikun Zhang Xiyu Liu Yongxiang Zhao Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver |
| description |
Abstract Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs. |
| format |
article |
| author |
Liping Zhong Yong Huang Jian He Nuo Yang Banghao Xu Yun Ma Junjie Liu Chao Tang Chengpiao Luo Pan Wu Zongqiang Lai Yu Huo Tao Lu Dongni Huang Wenlin Gong Lu Gan Yiqun Luo Zhikun Zhang Xiyu Liu Yongxiang Zhao |
| author_facet |
Liping Zhong Yong Huang Jian He Nuo Yang Banghao Xu Yun Ma Junjie Liu Chao Tang Chengpiao Luo Pan Wu Zongqiang Lai Yu Huo Tao Lu Dongni Huang Wenlin Gong Lu Gan Yiqun Luo Zhikun Zhang Xiyu Liu Yongxiang Zhao |
| author_sort |
Liping Zhong |
| title |
Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver |
| title_short |
Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver |
| title_full |
Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver |
| title_fullStr |
Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver |
| title_full_unstemmed |
Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver |
| title_sort |
generation of in situ crispr-mediated primary and metastatic cancer from monkey liver |
| publisher |
Nature Publishing Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/3966e94a00e04700bdb552809b5edfc5 |
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