Journal ArticleDOI
Treatment of HCV Infection by Targeting MicroRNA
Harry L.A. Janssen,Hendrik W. Reesink,Eric Lawitz,Stefan Zeuzem,Maribel Rodriguez-Torres,Keyur Patel,Adriaan J. van der Meer,Amy K. Patick,Alice Chen,Yi Zhou,Robert Persson,Barney D King,Sakari Kauppinen,Arthur A. Levin,Michael R. Hodges +14 more
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TLDR
The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance.Abstract:
Background The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid–modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function. Methods In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period. They were followed until 18 weeks after randomization. Results Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy. In the miravirsen groups, the mean maximum reduction in HCV RNA level (log10 IU per milliliter) from baseline was 1.2 (P=...read more
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Non-coding RNA in hepatocellular carcinoma: Mechanisms, biomarkers and therapeutic targets.
Marcel Klingenberg,Marcel Klingenberg,Marcel Klingenberg,Akiko Matsuda,Sven Diederichs,Tushar Patel +5 more
TL;DR: Examples of the functions of ncRNAs in liver cancer and their potential use for the detection and treatment of liver cancer are reviewed.
Journal ArticleDOI
MicroRNA in cardiovascular biology and disease.
TL;DR: In this paper, a review discusses emerging functions of miRNAs in cardiogenesis, heart regeneration and the pathophysiology of cardiovascular diseases, including myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation and atherosclerosis.
Journal ArticleDOI
Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice.
Oleg Butovsky,Mark P. Jedrychowski,Ron Cialic,Susanne Krasemann,Gopal Murugaiyan,Zain Fanek,David J. Greco,Pauline M. Wu,Camille Doykan,Olga Kiner,Robert Lawson,Matthew P. Frosch,Nathalie Pochet,Rachid El Fatimy,Anna M. Krichevsky,Steven P. Gygi,Hans Lassmann,James D. Berry,Merit Cudkowicz,Howard L. Weiner +19 more
TL;DR: To investigate miR‐155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis, the objective is to establish an experimental procedure and establish a EMT‐naïve mice model for the disease.
Journal ArticleDOI
Miravirsen (SPC3649) can inhibit the biogenesis of miR-122
Luca F R Gebert,Mario A. E. Rebhan,Silvia E. M. Crivelli,Rémy Denzler,Markus Stoffel,Jonathan Hall +5 more
TL;DR: New in vitro and cellular assays show that miravirsen binds to the stem-loop structure of pri- and pre-miR-122 with nanomolar affinity, and inhibits both Dicer- and Drosha-mediated processing of miR- 122 precursors.
Journal ArticleDOI
Pharmacology of Antisense Drugs
TL;DR: This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.
References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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Jan Krützfeldt,Nikolaus Rajewsky,Ravi Braich,Kallanthottathil G. Rajeev,Thomas Tuschl,Muthiah Manoharan,Markus Stoffel +6 more
TL;DR: It is shown that a novel class of chemically engineered oligonucleotides, termed ‘antagomirs’, are efficient and specific silencers of endogenous miRNA levels in mice and may represent a therapeutic strategy for silencing miRNAs in disease.
Journal ArticleDOI
Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA
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Journal ArticleDOI
Boceprevir for Untreated Chronic HCV Genotype 1 Infection
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