Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA‐122 levels without affecting other microRNAs in plasma

摘要: Summary Background MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus replication. Administration of miravirsen, anti-miR-122 oligonucleotide, resulted in a dose dependent and prolonged decrease HCV RNA levels chronic patients. Aim To assess the plasma level various miRNAs patients dosed with miravirsen. Methods We included 16 36 who received five injections either 3 mg/kg (n = 4), 5 7 4) miravirsen or placebo over 4-week period double-blind, randomised phase 2a study. Plasma 179 were determined by qPCR compared between placebo. Results Median miR-122 at baseline receiving was 3.9 × 103 to 1.3 104 copies/4 μL placebo-dosed (P 0.68). At week 1, 4, 6 10/12, had respectively median 72-fold, 174-fold, 1109-fold 552-fold lower expression than 0.001, as placebo). 4 dosing, miRNA-profiling demonstrated significant miR-210 miR-532-5p (3.0 4.7-fold respectively). However, subsequent longitudinal analysis showed no differences throughout study period. Conclusions We substantial miravirsen. other not significantly affected antagonising miR-122.