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Here we show that nuclear factor-kappa B (NF-\u03baB) mediates the leaky expression of Ad genes from the Ad vector genome and that the inhibition of NF-\u03baB leads to the suppression of Ad gene expression and hepatotoxicities following transduction with Ad vectors. Activation of NF-\u03baB by recombinant tumor necrosis factor (TNF)-\u03b1 significantly enhanced the leaky expression of Ad genes. More than 50% suppression of the Ad gene expression was found by inhibitors of NF-\u03baB signaling and siRNA-mediated knockdown of NF-\u03baB. Similar results were found when cells were infected with wild-type Ad. Compared with a conventional Ad vector, an Ad vector expressing a dominant-negative I\u03baB\u03b1 (Adv-CADNI\u03baB\u03b1), which is a negative regulator of NF-\u03baB, mediated approximately 70% suppression of the leaky expression of Ad genes in the liver. Adv-CADNI\u03baB\u03b1 did not induce apparent hepatotoxicities. These results indicate that inhibition of NF-\u03baB leads to suppression of Ad vector-mediated tissue damages <jats:italic>via<\/jats:italic> not only suppression of inflammatory responses but also reduction in the leaky expression of Ad genes.<\/jats:p>","DOI":"10.1038\/srep19922","type":"journal-article","created":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T11:21:45Z","timestamp":1453893705000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["NF-\u03baB promotes leaky expression of adenovirus genes in a replication-incompetent adenovirus vector"],"prefix":"10.1038","volume":"6","author":[{"given":"M.","family":"Machitani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Wakabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Nakatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tachibana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Mizuguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,27]]},"reference":[{"key":"BFsrep19922_CR1","doi-asserted-by":"publisher","first-page":"S164","DOI":"10.1002\/jgm.496","volume":"6","author":"C Volpers","year":"2004","unstructured":"Volpers, C. & Kochanek, S. 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