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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Adeno-associated virus-mediated microRNA delivery and therapeutics.
TL;DR: In this paper, the authors review currently used methods of altering miRNA activity in vivo and focus on the delivery of miRNAs and miRNA inhibitors using recombinant adeno-associated virus (rAAV).
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Hepatitis C virus infection: establishment of chronicity and liver disease progression.
TL;DR: Understanding the mechanisms for establishment of chronic HCV infection and liver disease progression at the molecular level should aid in developing strategies for additional effective therapies against HCV mediated liver disease progressions.
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MicroRNAs: New therapeutic targets for intestinal barrier dysfunction.
TL;DR: A review of the most recent state-of-the-art research on miRNAs in intestinal barrier dysfunction is provided.
Journal ArticleDOI
HBx Down-Regulated Gld2 Plays a Critical Role in HBV-Related Dysregulation of miR-122
Feng Peng,Xinqiang Xiao,Yongfang Jiang,Kaizhong Luo,Yi Tian,Milin Peng,Min Zhang,Yun Xu,Guozhong Gong +8 more
TL;DR: HBx is a critical protein derived from HBV, which regulates miR-122 via down-regulating Gld2, which was the most down-regulated microRNA in HepG2.
Journal ArticleDOI
MicroRNAs in kidney transplantation
Julia Wilflingseder,Roman Reindl-Schwaighofer,Judith Sunzenauer,Alexander Kainz,Andreas Heinzel,Bernd Mayer,Rainer Oberbauer +6 more
TL;DR: The basis of the recent ncRNA revolution is summarized and its implication for kidney transplantation is summarized.
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.
Journal ArticleDOI
The functions of animal microRNAs
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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
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
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