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Administration of miravirsen, an anti\u2010miR\u2010122 oligonucleotide, resulted in a dose dependent and prolonged decrease in <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> levels in chronic hepatitis C patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To assess the plasma level of various mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s in patients dosed with miravirsen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 16 of 36 chronic hepatitis C patients who received five injections of either 3 mg\/kg (<jats:italic>n<\/jats:italic> = 4), 5 mg\/kg (<jats:italic>n<\/jats:italic> = 4), 7 mg\/kg (<jats:italic>n<\/jats:italic> = 4) miravirsen or placebo (<jats:italic>n<\/jats:italic> = 4) over a 4\u2010week period in a double\u2010blind, randomised phase 2a study. Plasma levels of 179 mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s were determined by <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> and compared between patients dosed with miravirsen or placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Median plasma miR\u2010122 level at baseline in patients receiving miravirsen was 3.9 \u00d7 10<jats:sup>3<\/jats:sup> compared to 1.3 \u00d7 10<jats:sup>4<\/jats:sup> copies\/4 \u03bcL in placebo\u2010dosed patients (<jats:italic>P<\/jats:italic> = 0.68). At week 1, 4, 6 and 10\/12, patients dosed with miravirsen had respectively a median 72\u2010fold, 174\u2010fold, 1109\u2010fold and 552\u2010fold lower expression of miR\u2010122 than at baseline (<jats:italic>P<\/jats:italic> = 0.001, as compared to patients receiving placebo). At week 4 of dosing, mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010profiling demonstrated a significant lower expression of miR\u2010210 and miR\u2010532\u20105p compared to baseline (3.0 and 4.7\u2010fold lower respectively). However, subsequent longitudinal analysis showed no significant differences in miR\u2010210 and miR\u2010532\u20105p plasma levels throughout the study period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated a substantial and prolonged decrease in plasma miR\u2010122 levels in patients dosed with miravirsen. Plasma levels of other mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s were not significantly affected by antagonising miR\u2010122.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13432","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T02:03:31Z","timestamp":1445911411000},"page":"102-113","source":"Crossref","is-referenced-by-count":157,"title":["Miravirsen dosing in chronic hepatitis C patients results in decreased micro<scp>RNA<\/scp>\u2010122 levels without affecting other micro<scp>RNA<\/scp>s in plasma"],"prefix":"10.1111","volume":"43","author":[{"given":"M. H.","family":"van der Ree","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam The Netherlands"},{"name":"Department of Experimental Immunology Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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