{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T19:35:25Z","timestamp":1788377725690,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T00:00:00Z","timestamp":1210550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>RNA interference based therapeutic approaches hold promise for the treatment of patients chronically infected with hepatitis B virus (HBV). To conquer HBV infection, long\u2010term suppression of target transcripts in all hepatocytes without toxic effects may be required. The present study explored gene\u2010deleted adenoviral vectors (GD\u2010AdV) lacking all viral coding sequences for delivery of the previously described short hairpin RNA (shRNA) HBVU6no.2, which was demonstrated to result in post\u2010transcriptional knock\u2010down of HBV transcripts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established conditions for shRNA delivery expressed from GD\u2010AdV <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> and observed up to 96% shRNA\u2010mediated knockdown of luciferase expressed in mouse liver. To investigate <jats:italic>in vivo<\/jats:italic> efficacy of HBVU6no.2 expressed from a GD\u2010AdV, we explored a transient and a transgenic mouse model for HBV infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed an up to 68% drop in serum HBV surface antigen (HBsAg) levels in the transient and the transgenic mouse model for HBV infection, respectively. Interestingly, we detected an up to 86% drop in HBsAg levels in both animal models after administration of a control GD\u2010AdV encoding \u03b2\u2010galactosidase. In concordance with reduced serum HBsAg levels, we observed reduced HBV replication as demonstrated by Southern blot analysis of HBV genomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study demonstrates that GD\u2010AdV can be used against HBV infection but the design of DNA sequences including shRNAs contained in the vector and virus\u2013host interactions during superinfection needs to be carefully considered. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1207","type":"journal-article","created":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T08:17:15Z","timestamp":1210580235000},"page":"878-889","source":"Crossref","is-referenced-by-count":20,"title":["Exploring gene\u2010deleted adenoviral vectors for delivery of short hairpin RNAs and reduction of hepatitis B virus infection in mice"],"prefix":"10.1002","volume":"10","author":[{"given":"Christina","family":"Rauschhuber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix H.","family":"Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia 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