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 in T helper cell differentiation and plasticity.
TL;DR: This work focuses on miRNAs known to be involved in regulating the biology of CD4 T helper lymphocytes, a type of immune cell that is dysregulated in autoimmune and inflammatory disorders.
Journal ArticleDOI
The Crosstalk of miRNA and Oxidative Stress in the Liver: From Physiology to Pathology and Clinical Implications.
Eckhard Klieser,Christian Mayr,Tobias Kiesslich,Till Wissniowski,Pietro Di Fazio,Daniel Neureiter,Daniel Neureiter,Matthias Ocker +7 more
TL;DR: This literature review focuses on the changes at the miRNA level, the formation and impact of reactive oxygen species and the crosstalk between those factors.
Journal ArticleDOI
Cross-regulation between cytokine and microRNA pathways in T cells.
TL;DR: How cytokines regulate miRNA expression, and how specific miRNAs control cytokine production in T cells is summarized, which will have key implications for immune modulation and treatment of autoimmune pathology.
Journal ArticleDOI
Prospects of miRNA-based therapy for pancreatic cancer.
TL;DR: The current review attempts to summarize the advances in the field and assesses the prospects for miRNA profiling and targeting in aiding PC treatment and concludes that successful targeting of miRNAs as therapeutic agents could likely yield dramatic results.
Journal ArticleDOI
The emerging roles of MicroRNAs in autism spectrum disorders.
Julien Fregeac,Julien Fregeac,Laurence Colleaux,Laurence Colleaux,Lam Son Nguyen,Lam Son Nguyen +5 more
TL;DR: Recent studies providing genetic and molecular links between miRNA deregulation and ASD pathophysiology are reviewed, highlighting the potential of miRNAs as both biomarkers and therapeutic tools in ASD.
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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