{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:01:44Z","timestamp":1790791304845,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T00:00:00Z","timestamp":1533168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T00:00:00Z","timestamp":1533168000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570172"],"award-info":[{"award-number":["81570172"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["16ZR1428600"],"award-info":[{"award-number":["16ZR1428600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2018,12]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n \n This study explored whether\n TALEN<\/jats:styled-content>\n s\u2010mediated non\u2010homologous end joining (\n NHEJ<\/jats:styled-content>\n ) targeting the mutation site can correct the aberrant \u03b2\u2010globin\n RNA<\/jats:styled-content>\n splicing, and ameliorate the \u03b2\u2010thalassaemia phenotype in \u03b2\n 654<\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Material and methods<\/jats:title>\n \n TALEN<\/jats:styled-content>\n s vectors targeted to the human \u03b2\u2010globin gene (\n \n HBB<\/jats:styled-content>\n <\/jats:italic>\n ) I\n VS<\/jats:styled-content>\n 2\u2010654C >T mutation in a mouse model were constructed and selected to generate double heterozygous\n TALEN<\/jats:styled-content>\n s\n +<\/jats:sup>\n \/\u03b2\n 654<\/jats:sup>\n mice. The gene editing and off\u2010target effects were analysed by sequencing analysis. \u03b2\u2010globin expression was identified by\n RT<\/jats:styled-content>\n \u2010\n PCR<\/jats:styled-content>\n and Western blot analysis. Various clinical indices including haematologic parameters and tissue pathology were examined to determine the therapeutic effect in these\n TALEN<\/jats:styled-content>\n s\n +<\/jats:sup>\n \/\u03b2\n 654<\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Sequencing analysis revealed that the\n \n HBB<\/jats:styled-content>\n <\/jats:italic>\n IVS<\/jats:styled-content>\n 2\u2010654C >T point mutation was deleted in over 50% of the\n TALEN<\/jats:styled-content>\n s\n +<\/jats:sup>\n \/\u03b2\n 654<\/jats:sup>\n mice tested, and off\u2010target effects were not detected.\n RT<\/jats:styled-content>\n \u2010\n PCR<\/jats:styled-content>\n and Western blot analysis confirmed the expression of normal \u03b2\u2010globin in\n TALEN<\/jats:styled-content>\n s\n +<\/jats:sup>\n \/\u03b2\n 654<\/jats:sup>\n mice. The haematologic parameters were significantly improved as compared with their affected littermates. The proportion of nucleated cells in bone marrow was considerably decreased, splenomegaly with extramedullary haematopoiesis was reduced, and significant decreases in iron deposition were seen in spleen and liver of the\n TALEN<\/jats:styled-content>\n s\n +<\/jats:sup>\n \/\u03b2\n 654<\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These results suggest effective treatment of the anaemia phenotype in\n TALEN<\/jats:styled-content>\n s\n +<\/jats:sup>\n \/\u03b2\n 654<\/jats:sup>\n mice following deletion of the mutation site by\n TALEN<\/jats:styled-content>\n s, demonstrating a simple and straightforward strategy for gene therapy of \u03b2\n 654<\/jats:sup>\n \u2010thalassaemia in the future.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cpr.12491","type":"journal-article","created":{"date-parts":[[2018,8,5]],"date-time":"2018-08-05T16:57:29Z","timestamp":1533488249000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Treatment of \u03b2\n 654<\/sup>\n \u2010thalassaemia by\n TALEN<\/scp>\n s in a mouse model"],"prefix":"10.1111","volume":"51","author":[{"given":"Yudan","family":"Fang","sequence":"first","affiliation":[{"name":"Shanghai Children's Hospital Shanghai Institute of Medical Genetics Shanghai Jiao Tong University Shanghai China"},{"name":"Department of Histo\u2010Embryology, Genetics and Developmental Biology Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Key Laboratory of Embryo Molecular Biology Ministry of Health & Shanghai Key Laboratory of Embryo and Reproduction Engineering Shanghai 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