Cell stem cell · 2014
TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Liu Hailiang, Chen Yongchang, Niu Yuyu, Zhang Kunshan, Kang Yu, Ge Weihong, Liu Xiaojing, Zhao Enfeng, Wang Chencheng, Lin Shaoyun, Jing Bo, Si Chenyang, Lin Quan, Chen Xiaoying, Lin Haijun, Pu Xiuqiong, Wang Yingying, Qin Binlian, Wang Fang, Wang Hong, Si Wei, Zhou Jing, Tan Tao, Li Tianqing, Ji Shaohui, Xue Zhigang, Luo Yuping, Cheng Liming, Zhou Qi, Li Siguang, Sun Yi Eve, Ji Weizhi
Аннотация
Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in nonhuman primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett syndrome (RTT) gene, methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. Microinjection of MECP2-targeting TALEN plasmids into rhesus and cynomolgus zygotes leads to effective gene editing of MECP2 with no detected off-target mutagenesis. Male rhesus (2) and cynomolgous (1) fetuses carrying MECP2 mutations in various tissues including testes were miscarried during midgestation, consistent with RTT-linked male embryonic lethality in humans. One live delivery of a female cynomolgus monkey occurred after 162 days of gestation, with abundant MECP2 mutations in peripheral tissues. We conclude that TALEN-mediated mutagenesis can be an effective tool for genetic modeling of human disease in nonhuman primates.