{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:59:13Z","timestamp":1791331153414,"version":"4.3.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2011,8,9]],"date-time":"2011-08-09T00:00:00Z","timestamp":1312848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Hereditary tyrosinemia type I (HT1) results in hepatic failure, cirrhosis, and hepatocellular carcinoma (HCC) early in childhood and is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (FAH). In a novel approach we used the chimeric adeno-associated virus DJ serotype (AAV-DJ) and homologous recombination to target and disrupt the porcine<\/jats:bold>\n                                 <jats:bold>\n                                    Fah\n                                 <\/jats:bold>\n                                 <jats:bold>gene. AAV-DJ is an artificial chimeric AAV vector containing hybrid capsid sequences from three naturally occurring serotypes (AAV2, 8, and 9). The AAV-DJ vector was used to deliver the knockout construct to fetal pig fibroblasts with an average knockout targeting frequency of 5.4%. Targeted<\/jats:bold>\n                                 <jats:bold>\n                                    Fah\n                                 <\/jats:bold>\n                                 <jats:bold>-null heterozygote fibroblasts were used as nuclear donors for somatic cell nuclear transfer (SCNT) to porcine oocytes and multiple viable<\/jats:bold>\n                                 <jats:bold>\n                                    Fah\n                                 <\/jats:bold>\n                                 <jats:bold>-null heterozygote pigs were generated.<\/jats:bold>\n                                 <jats:bold>\n                                    Fah\n                                 <\/jats:bold>\n                                 <jats:bold>-null heterozygotes were phenotypically normal, but had decreased<\/jats:bold>\n                                 <jats:bold>\n                                    Fah\n                                 <\/jats:bold>\n                                 <jats:bold>transcriptional and enzymatic activity compared to wildtype animals. Conclusion: This study is the first to use a recombinant chimeric AAV vector to knockout a gene in porcine fibroblasts for the purpose of SCNT. In using the AAV-DJ vector we observed targeting frequencies that were higher than previously reported with other naturally occurring serotypes. We expect that the subsequent generation of FAH-null homozygote pigs will serve as a significant advancement for translational research in the areas of metabolic liver disease, cirrhosis, and HCC. (Hepatology 2011;)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.24490","type":"journal-article","created":{"date-parts":[[2011,6,14]],"date-time":"2011-06-14T14:59:16Z","timestamp":1308063556000},"page":"1351-1359","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":75,"title":["Efficient production of Fah -null heterozygote pigs by chimeric adeno-associated virus-mediated gene knockout and somatic cell nuclear transfer"],"prefix":"10.1097","volume":"54","author":[{"given":"Raymond D.","family":"Hickey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph B.","family":"Lillegard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis 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