{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:17:07Z","timestamp":1762161427541},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Key R&D Program of China","award":["2016YFA0101401","2016YFC0105703"],"award-info":[{"award-number":["2016YFA0101401","2016YFC0105703"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biotechnol"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12896-018-0494-2","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T14:03:03Z","timestamp":1547560983000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Homologous recombination-mediated targeted integration in monkey embryos using TALE nucleases"],"prefix":"10.1186","volume":"19","author":[{"given":"Chu","family":"Chu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaohui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyang","family":"Si","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongchang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weizhi","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyu","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,1,15]]},"reference":[{"issue":"3","key":"494_CR1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.neuron.2015.03.021","volume":"86","author":"JC Izpisua Belmonte","year":"2015","unstructured":"Izpisua Belmonte JC, et al. Brains, genes, and primates. Neuron. 2015;86(3):617\u201331.","journal-title":"Neuron"},{"issue":"4","key":"494_CR2","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.cell.2014.01.027","volume":"156","author":"Y Niu","year":"2014","unstructured":"Niu Y, et al. Generation of gene-modified cynomolgus monkey via Cas9\/RNA-mediated gene targeting in one-cell embryos. Cell. 2014;156(4):836\u201343.","journal-title":"Cell"},{"key":"494_CR3","doi-asserted-by":"crossref","unstructured":"Chen, Y., et al., Modeling Rett syndrome using TALEN-edited MECP2 mutant Cynomolgus monkeys. Cell, 2017. 169(5): p. 945\u2013955.e10.","DOI":"10.1016\/j.cell.2017.04.035"},{"issue":"3","key":"494_CR4","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s12264-014-1434-8","volume":"30","author":"Z Liu","year":"2014","unstructured":"Liu Z, et al. Generation of a monkey with MECP2 mutations by TALEN-based gene targeting. Neurosci Bull. 2014;30(3):381\u20136.","journal-title":"Neurosci Bull"},{"issue":"25","key":"494_CR5","doi-asserted-by":"publisher","first-page":"7255","DOI":"10.1093\/hmg\/ddv425","volume":"24","author":"Y Kang","year":"2015","unstructured":"Kang Y, et al. CRISPR\/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH. Hum Mol Genet. 2015;24(25):7255\u201364.","journal-title":"Hum Mol Genet"},{"issue":"12","key":"494_CR6","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1126\/science.291.5502.309","volume":"291","author":"AWS Chan","year":"2001","unstructured":"Chan AWS, Chong KY, Martinovich C, Simerly C, Schatten G. Transgenic Monkeys Produced by Retroviral Gene Transfer into Mature Oocytes. Science. 2001;291(12):309\u201312.","journal-title":"Science"},{"issue":"7197","key":"494_CR7","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/nature06975","volume":"453","author":"SH Yang","year":"2008","unstructured":"Yang SH, et al. Towards a transgenic model of Huntington's disease in a non-human primate. Nature. 2008;453(7197):921\u20134.","journal-title":"Nature"},{"issue":"1","key":"494_CR8","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ymeth.2009.05.007","volume":"49","author":"AW Chan","year":"2009","unstructured":"Chan AW, Yang SH. Generation of transgenic monkeys with human inherited genetic disease. Methods. 2009;49(1):78\u201384.","journal-title":"Methods"},{"issue":"3","key":"494_CR9","first-page":"22","volume":"6","author":"AA Nemudryi","year":"2014","unstructured":"Nemudryi AA, Valetdinova KR, Medvedev SP, Zakian SM. TALEN and CRISPRCas Genome Editing Systems Tools of Discovery. Acta Nat. 2014;6(3):22.","journal-title":"Acta Nat"},{"issue":"8","key":"494_CR10","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1177\/1535370215584932","volume":"240","author":"J Pu","year":"2015","unstructured":"Pu J, et al. Utilization of TALEN and CRISPR\/Cas9 technologies for gene targeting and modification. Exp Biol Med (Maywood). 2015;240(8):1065\u201370.","journal-title":"Exp Biol Med (Maywood)"},{"issue":"5","key":"494_CR11","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1002\/aur.1945","volume":"11","author":"H Zhao","year":"2018","unstructured":"Zhao H, Jiang YH, Zhang YQ. Modeling autism in non-human primates: opportunities and challenges. Autism Res. 2018;11(5):686\u201394.","journal-title":"Autism Res"},{"issue":"2","key":"494_CR12","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.expneurol.2008.04.027","volume":"212","author":"F Ding","year":"2008","unstructured":"Ding F, et al. Development of a stable, early stage unilateral model of Parkinson's disease in middle-aged rhesus monkeys. Exp Neurol. 2008;212(2):431\u20139.","journal-title":"Exp Neurol"},{"issue":"13","key":"494_CR13","doi-asserted-by":"publisher","first-page":"3764","DOI":"10.1093\/hmg\/ddv120","volume":"24","author":"Y Chen","year":"2015","unstructured":"Chen Y, et al. Functional disruption of the dystrophin gene in rhesus monkey using CRISPR\/Cas9. Hum Mol Genet. 2015;24(13):3764\u201374.","journal-title":"Hum Mol Genet"},{"key":"494_CR14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-1-4939-2932-0_3","volume":"1338","author":"DG Ousterout","year":"2016","unstructured":"Ousterout DG, Gersbach CA. The development of TALE nucleases for biotechnology. Methods Mol Biol. 2016;1338:27\u201342.","journal-title":"Methods Mol Biol"},{"issue":"1","key":"494_CR15","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/nprot.2015.140","volume":"11","author":"T Sakuma","year":"2016","unstructured":"Sakuma T, et al. MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems. Nat Protoc. 2016;11(1):118\u201333.","journal-title":"Nat Protoc"},{"issue":"6","key":"494_CR16","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1038\/mt.2013.56","volume":"21","author":"MJ Osborn","year":"2013","unstructured":"Osborn MJ, et al. TALEN-based gene correction for epidermolysis bullosa. Mol Ther. 2013;21(6):1151\u20139.","journal-title":"Mol Ther"},{"issue":"4","key":"494_CR17","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1039\/c2mb05461b","volume":"8","author":"N Sun","year":"2012","unstructured":"Sun N, et al. Optimized TAL effector nucleases (TALENs) for use in treatment of sickle cell disease. Mol BioSyst. 2012;8(4):1255\u201363.","journal-title":"Mol BioSyst"},{"issue":"2","key":"494_CR18","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1093\/nar\/gkt947","volume":"42","author":"RA Voit","year":"2014","unstructured":"Voit RA, et al. Nuclease-mediated gene editing by homologous recombination of the human globin locus. Nucleic Acids Res. 2014;42(2):1365\u201378.","journal-title":"Nucleic Acids Res"},{"issue":"48","key":"494_CR19","doi-asserted-by":"publisher","first-page":"34671","DOI":"10.1074\/jbc.M113.496174","volume":"288","author":"N Ma","year":"2013","unstructured":"Ma N, et al. Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free beta-thalassemia induced pluripotent stem cells. J Biol Chem. 2013;288(48):34671\u20139.","journal-title":"J Biol Chem"},{"issue":"6","key":"494_CR20","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1002\/hep.26237","volume":"57","author":"SM Choi","year":"2013","unstructured":"Choi SM, et al. Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology. 2013;57(6):2458\u201368.","journal-title":"Hepatology"},{"issue":"19","key":"494_CR21","doi-asserted-by":"publisher","first-page":"3807","DOI":"10.1242\/dev.108019","volume":"141","author":"J Shin","year":"2014","unstructured":"Shin J, Chen J, Solnica-Krezel L. Efficient homologous recombination-mediated genome engineering in zebrafish using TALE nucleases. Development. 2014;141(19):3807\u201318.","journal-title":"Development"},{"key":"494_CR22","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12896-016-0234-4","volume":"16","author":"VT Chu","year":"2016","unstructured":"Chu VT, et al. Efficient generation of Rosa26 knock-in mice using CRISPR\/Cas9 in C57BL\/6 zygotes. BMC Biotechnol. 2016;16:4.","journal-title":"BMC Biotechnol"},{"key":"494_CR23","doi-asserted-by":"publisher","first-page":"25161","DOI":"10.1038\/srep25161","volume":"6","author":"D Yang","year":"2016","unstructured":"Yang D, et al. Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression. Sci Rep. 2016;6:25161.","journal-title":"Sci Rep"},{"key":"494_CR24","doi-asserted-by":"publisher","first-page":"10482","DOI":"10.1038\/srep10482","volume":"5","author":"C Cui","year":"2015","unstructured":"Cui C, et al. Gene targeting by TALEN-induced homologous recombination in goats directs production of beta-lactoglobulin-free, high-human lactoferrin milk. Sci Rep. 2015;5:10482.","journal-title":"Sci Rep"},{"key":"494_CR25","doi-asserted-by":"publisher","first-page":"24360","DOI":"10.1038\/srep24360","volume":"6","author":"M Wu","year":"2016","unstructured":"Wu M, et al. Rosa26-targeted sheep gene knock-in via CRISPR-Cas9 system. Sci Rep. 2016;6:24360.","journal-title":"Sci Rep"},{"key":"494_CR26","unstructured":"Haibo Wu , Y Wang , Yan Zhang , Mingqi Yang , Jiaxing Lv , Jun Liu , and Yong Zhang, TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. PNAS march 2, 2015 p. March 2, 2015."},{"issue":"1","key":"494_CR27","doi-asserted-by":"publisher","first-page":"e0146562","DOI":"10.1371\/journal.pone.0146562","volume":"11","author":"S Lai","year":"2016","unstructured":"Lai S, et al. Generation of Knock-in pigs carrying Oct4-tdTomato reporter through CRISPR\/Cas9-mediated genome engineering. PLoS One. 2016;11(1):e0146562.","journal-title":"PLoS One"},{"issue":"3","key":"494_CR28","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/cr.2018.9","volume":"28","author":"X Yao","year":"2018","unstructured":"Yao X, et al. Generation of knock-in cynomolgus monkey via CRISPR\/Cas9 editing. Cell Res. 2018;28(3):379\u201382.","journal-title":"Cell Res"},{"issue":"3","key":"494_CR29","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/cr.2018.10","volume":"28","author":"Y Cui","year":"2018","unstructured":"Cui Y, et al. Generation of a precise Oct4-hrGFP knockin cynomolgus monkey model via CRISPR\/Cas9-assisted homologous recombination. Cell Res. 2018;28(3):383\u20136.","journal-title":"Cell Res"},{"issue":"9","key":"494_CR30","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/nbt.1562","volume":"27","author":"D Hockemeyer","year":"2009","unstructured":"Hockemeyer D, et al. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol. 2009;27(9):851\u20137.","journal-title":"Nat Biotechnol"},{"issue":"10","key":"494_CR31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109728","volume":"9","author":"L Quan","year":"2014","unstructured":"Quan L, et al. Establishment of a rabbit Oct4 promoter-based EGFP reporter system. PLoS One. 2014;9(10):e109728.","journal-title":"PLoS One"},{"key":"494_CR32","doi-asserted-by":"crossref","unstructured":"Kosicki M, Tomberg K, Bradley A. Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol. 2018; 36(8):765-71.","DOI":"10.1038\/nbt.4192"},{"key":"494_CR33","doi-asserted-by":"crossref","unstructured":"Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J. CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response. Nat Med. 2018;24(7):927-30.","DOI":"10.1038\/s41591-018-0049-z"},{"issue":"6","key":"494_CR34","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1016\/j.cell.2013.08.022","volume":"154","author":"H Yang","year":"2013","unstructured":"Yang H, et al. One-step generation of mice carrying reporter and conditional alleles by CRISPR\/Cas-mediated genome engineering. Cell. 2013;154(6):1370\u20139.","journal-title":"Cell"},{"issue":"8","key":"494_CR35","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.1648","volume":"8","author":"MT Certo","year":"2011","unstructured":"Certo MT, et al. Tracking genome engineering outcome at individual DNA breakpoints. Nat Methods. 2011;8(8):671\u20136.","journal-title":"Nat Methods"},{"issue":"7","key":"494_CR36","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/nbt.4166","volume":"36","author":"B Gu","year":"2018","unstructured":"Gu B, Posfai E, Rossant J. Efficient generation of targeted large insertions by microinjection into two-cell-stage mouse embryos. Nat Biotechnol. 2018;36(7):632\u20137.","journal-title":"Nat Biotechnol"},{"key":"494_CR37","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/B978-0-12-418687-3.00018-5","volume":"529","author":"PA Longo","year":"2013","unstructured":"Longo PA, et al. Transient mammalian cell transfection with polyethylenimine (PEI). Methods Enzymol. 2013;529:227\u201340.","journal-title":"Methods Enzymol"},{"issue":"41","key":"494_CR38","doi-asserted-by":"publisher","first-page":"17663","DOI":"10.1073\/pnas.1006563107","volume":"107","author":"Y Niu","year":"2010","unstructured":"Niu Y, et al. Transgenic rhesus monkeys produced by gene transfer into early-cleavage-stage embryos using a simian immunodeficiency virus-based vector. Proc Natl Acad Sci U S A. 2010;107(41):17663\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"494_CR39","doi-asserted-by":"publisher","first-page":"e82","DOI":"10.1093\/nar\/gkr218","volume":"39","author":"T Cermak","year":"2011","unstructured":"Cermak T, et al. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 2011;39(12):e82.","journal-title":"Nucleic Acids Res"}],"container-title":["BMC Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12896-018-0494-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12896-018-0494-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12896-018-0494-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T14:14:06Z","timestamp":1580739246000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbiotechnol.biomedcentral.com\/articles\/10.1186\/s12896-018-0494-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,15]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["494"],"URL":"https:\/\/doi.org\/10.1186\/s12896-018-0494-2","relation":{},"ISSN":["1472-6750"],"issn-type":[{"value":"1472-6750","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,15]]},"assertion":[{"value":"31 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The cynomolgus monkey (<i>Macaca fascicularis<\/i>) involved in this study is accredited by AAALAC International and all experimental protocols were approved in advance by the Institutional Animal Care and Use Committee of Yunnan Key Laboratory of Primate Biomedical Research.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"7"}}