@article{b9260ab01de3475384aacf09f70781c4,
title = "TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys",
abstract = "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.",
author = "Hailiang Liu and Yongchang Chen and Yuyu Niu and Kunshan Zhang and Yu Kang and Weihong Ge and Xiaojing Liu and Enfeng Zhao and Chencheng Wang and Shaoyun Lin and Bo Jing and Chenyang Si and Quan Lin and Xiaoying Chen and Haijun Lin and Xiuqiong Pu and Yingying Wang and Binlian Qin and Fang Wang and Hong Wang and Wei Si and Jing Zhou and Tao Tan and Tianqing Li and Shaohui Ji and Zhigang Xue and Yuping Luo and Liming Cheng and Qi Zhou and Siguang Li and Sun, {Yi Eve} and Weizhi Ji",
note = "Funding Information: The authors would like to acknowledge the Division of Animal Resources at the Kunming Biomed International for providing expertise and services that contributed to this project. This work was supported by the Major State Basic Research Development Program of China (973 Program) (No. 2012CBA01300, 2012CB966900, 2010CB945202, and 2011CB965103), the National High Technology Research and Development Program of China (863 Program) (No. 2012AA020701), Yunnan Innovation Talents of Science and Technology (No. 2012HA013), the National Natural Science Foundation of China (31271599, U1302227, 31301058, 90919057, 31271371, and 91319309), Key program for the basic research of the science and technology commission of Shanghai (13JC1407102), “Western Light” Talents Training Program of CAS and Yunnan Academic Leaders and Reserve Personnel, and Young Talents Training Program of Tongji University. We also acknowledge grants from NIH (P01 GM081621-01A1 and 1R01MH082068-01A2) and CIRM (RB3-02129) to Y.E.S. and the Transcriptome and Epigenetics Core of Center for Study of Opioid Receptors and Drugs of Abuse (CSORDA center grant: NIH-P50DA005010) and Intellectual and Developmental Disabilities Research Center (IDDRC center grant: NIH-P30HD004612) at UCLA. ",
year = "2014",
month = mar,
day = "6",
doi = "10.1016/j.stem.2014.01.018",
language = "English",
volume = "14",
pages = "323--328",
journal = "Cell Stem Cell",
issn = "1934-5909",
number = "3",
}