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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MicroRNAs and metabolism crosstalk in energy homeostasis.
Olivier Dumortier,Olivier Dumortier,Olivier Dumortier,Charlotte Hinault,Emmanuel Van Obberghen +4 more
TL;DR: A challenging road lies ahead for defining the role of miRNAs in the pathogenesis of diseases such as diabetes and for establishing their usefulness as new medications and clinically reliable biomarkers.
Journal ArticleDOI
MicroRNA Therapeutics: the Next Magic Bullet?
Bridget Simonson,Saumya Das +1 more
TL;DR: The current knowledge of microRNA therapy is reviewed, and ways in which they can be utilized are discussed, and the current limitations in the field are discussed.
Journal ArticleDOI
miRNA sponges: soaking up miRNAs for regulation of gene expression
TL;DR: Combined with potent and versatile vector technologies, expression of custom‐designed sponges provides new means of managing miRNAs and soaking up miRNAAs for therapeutic regulation of gene expression.
Journal ArticleDOI
MicroRNAs in epilepsy: pathophysiology and clinical utility
David C. Henshall,Hajo M. Hamer,R. Jeroen Pasterkamp,David Goldstein,Jørgen Kjems,Jochen H. M. Prehn,Stephanie Schorge,Kai Lamottke,Felix Rosenow,Felix Rosenow +9 more
TL;DR: The latest findings provide a rich source of new miRNAs that appear to influence seizures or hippocampal pathology, but substantial challenges remain before their role in the pathogenesis, diagnosis, and treatment of epilepsy can be translated into clinical practice.
Journal ArticleDOI
Therapeutic nucleic acids: current clinical status.
Kannan Sridharan,Nithya J Gogtay +1 more
TL;DR: With their specificity, functional diversity and limited toxicity, therapeutic nucleic acids hold enormous promise, however, challenges that need to be addressed include targeted delivery, mass production at low cost, sustaining efficacy and minimizing off‐target toxicity.
References
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Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
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.
Journal ArticleDOI
The functions of animal microRNAs
TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
Journal ArticleDOI
Silencing of microRNAs in vivo with ‘antagomirs’
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
TL;DR: It is shown that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs, suggesting that miR -122 may present a target for antiviral intervention.
Journal ArticleDOI
Boceprevir for Untreated Chronic HCV Genotype 1 Infection
TL;DR: The addition of boceprevir to standard therapy with peginterferon–ribavirin, as com pared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection.
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