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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The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids
Judith Agudo,Albert Ruzo,Navpreet Tung,Hélène Salmon,Marylene Leboeuf,Daigo Hashimoto,Christian Becker,Lee Ann Garrett-Sinha,Alessia Baccarini,Miriam Merad,Brian D. Brown +10 more
TL;DR: The studies identify the miR-126–VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.
Journal ArticleDOI
microRNAs in Psoriasis.
Jason E. Hawkes,Giang Nguyen,Mayumi Fujita,Scott R. Florell,Kristina Callis Duffin,Gerald G. Krueger,Ryan M. O'Connell +6 more
TL;DR: A comprehensive review of what is known about microRNAs and their role in the pathogenesis of psoriasis is presented.
Journal ArticleDOI
RNA Therapeutics in Cardiovascular Disease.
TL;DR: Examples of microRNAs and long noncoding RNAs, which might be promising novel targets for treatment of cardiovascular diseases, such as heart failure, acute myocardial infarction, fibrosis, as well as atherosclerosis, are summarized.
Journal ArticleDOI
Epigenetics and depression: return of the repressed
TL;DR: Epigenetic modification of gene expression provides a mechanism for understanding the link between long-term effects of adverse life events and the changes in gene expression that are associated with depression.
Journal ArticleDOI
MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis
Wen Pan,Shu Zhu,Dai Dai,Zheng Liu,Dan Li,Bin Li,Nicola Gagliani,Yunjiang Zheng,Yuanjia Tang,Matthew T. Weirauch,Xiaoting Chen,Wei Zhu,Yue Wang,Bo Chen,Youcun Qian,Ying-Xuan Chen,Jing-Yuan Fang,Ronald Herbst,Laura Richman,Bahija Jallal,John B. Harley,Richard A. Flavell,Yihong Yao,Nan Shen +23 more
TL;DR: It is shown that miR-125a is downregulated in peripheral CD4(+) T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn's disease, and relevant autoimmune mouse models, and it is pointed to as a critical factor that controls autoimmune diseases by stabilizing Treg-mediated immune homeostasis.
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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