Science · 2009 · 1.6K citations · 18 references
Life SciencesInfectious DiseasesMolecular BiologyGene ExpressionMolecular VirologyVirologyAntiviral TherapyLiver DiseaseMicrorna BiologyRna InterferenceViral HepatitisViral Hepatitis TreatmentConserved MicrornasMicrorna TargetingMicrorna TherapeuticsMicrorna TherapyMicrorna-mediated Gene SilencingRegulatorsTherapeutic Gene SilencingViral Small Rna Silencing
MicroRNAs regulate cellular processes, and the highly conserved miR‑122 is essential for hepatitis C virus replication, yet current HCV therapies are limited by side effects and low efficacy. The study aimed to evaluate whether silencing miR‑122 could serve as a therapeutic strategy against HCV infection. They used a locked nucleic acid (LNA) oligonucleotide complementary to miR‑122 to inhibit its activity. In chimpanzees, LNA‑mediated miR‑122 silencing produced sustained symptom reduction and did not select for resistant viral strains.
Anti-MicroRNA Antiviral MicroRNAs (miRNAs) are small noncoding RNAs found in eukaryotes and viruses. They are critical regulators of a wide range of cellular processes. The highly conserved miRNA miR-122 is required for infection by hepatitis C virus (HCV), a leading cause of liver disease in humans. Present HCV treatment regimes can have serious side effects and are effective in only 50% of cases. In order to try to tackle HCV infection, Lanford et al. (p. 198 , published online 3 December) targeted miR-122 using a complementary locked nucleic acid (LNA) oligonucleotide. Treatment of chimpanzees infected by HCV with the LNA antagonist resulted in a long-term reduction of disease symptoms without the concomitant appearance of resistant strains of the virus.
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Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA
Catherine L. Jopling, MinKyung Yi, Alissa M. Lancaster et al. · Science · 2005 · 2.5K citations
LNA-mediated microRNA silencing in non-human primates
Joacim Elmén, Morten Lindow, Sylvia Schütz et al. · Nature · 2008 · 1.6K citations
Joacim Elmén, Morten Lindow, Asli Silahtaroglu et al. · Nucleic Acids Research · 2007 · 671 citations · Full text