{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:28:53Z","timestamp":1777552133430,"version":"3.51.4"},"reference-count":28,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>\n                    The shortage of human hepatocytes continues to be a significant limitation for the widespread application of hepatocyte transplantation and bioartificial liver (BAL) support therapy. Recombinant activation gene 2 (\n                    <jats:italic toggle=\"yes\">Rag2<\/jats:italic>\n                    ) and fumarylacetoacetate hydrolase (\n                    <jats:italic toggle=\"yes\">Fah<\/jats:italic>\n                    )-deficient mice could be highly repopulated with human hepatocytes. However,\n                    <jats:italic toggle=\"yes\">Fah<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">Rag2-<\/jats:italic>\n                    deficient mice can only produce up to 1\u2009\u00d7\u200910\n                    <jats:sup>8<\/jats:sup>\n                    human hepatocytes per mouse. We hypothesized that 2\u201310\u2009\u00d7\u200910\n                    <jats:sup>10<\/jats:sup>\n                    human hepatocytes can be produced per\n                    <jats:italic toggle=\"yes\">Fah<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">Rag2<\/jats:italic>\n                    -deficient pig, which is an adequate supply for hepatocyte transplantation and BAL therapy. In a novel approach, we used stably transfected Cas9 cells and single-guide RNA adenoviruses containing fluorescent reporters to enrich porcine cells with\n                    <jats:italic toggle=\"yes\">Fah<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">Rag2<\/jats:italic>\n                    dual gene mutations. This resulted in the construction of\n                    <jats:italic toggle=\"yes\">Fah\/Rag2<\/jats:italic>\n                    double knockout porcine iliac artery endothelial cells, which were subsequently used for generating\n                    <jats:italic toggle=\"yes\">Fah\/Rag2<\/jats:italic>\n                    -deficient pigs.\n                  <\/jats:p>","DOI":"10.1089\/dna.2018.4493","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T10:35:09Z","timestamp":1550140509000},"page":"314-321","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficient Generation of an\n                    <i>Fah\/Rag2<\/i>\n                    Dual-Gene Knockout Porcine Cell Line Using CRISPR\/Cas9 and Adenovirus"],"prefix":"10.1177","volume":"38","author":[{"given":"Mengyu","family":"Gao","sequence":"first","affiliation":[{"name":"Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"He","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihong","family":"Deng","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, West China School of Medicine, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, West China School of Medicine, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enjiang","family":"Lai","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, West China School of Medicine, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, West China School of Medicine, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laduona","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, West China School of Medicine, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Center, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangneng","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Center, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji","family":"Bao","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Bu","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan University, Chengdu, China."},{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, 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