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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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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MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
TL;DR: Recent advances in the understanding of miRNAs in cancer and in other diseases are described and the challenge of identifying the most efficacious therapeutic candidates is discussed and a perspective on achieving safe and targeted delivery of miRNA therapeutics is provided.
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MicroRNAs in cancer: biomarkers, functions and therapy.
TL;DR: The potential applications of microRNAs for the clinical assessment of patient outcome in cancer, as well as in cancer monitoring and therapy are reviewed.
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Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches
TL;DR: This review guides the reader through important aspects of non-coding RNA biology, including their biogenesis, mode of actions, physiological function, as well as their role in the disease context (such as in cancer or the cardiovascular system).
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MicroRNAs and other non-coding RNAs as targets for anticancer drug development
TL;DR: The roles of miRNAs and lncRNAs in cancer are summarized, with a focus on the recently identified novel mechanisms of action, and the current strategies in designing ncRNA-targeting therapeutics are discussed.
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Clinical relevance of circulating cell-free microRNAs in cancer
TL;DR: The latest developments in the use of circulating microRNAs as prognostic and predictive biomarkers are considered and their utility in personalized medicine is discussed.
References
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