Nature reviews. Drug discovery: News in brief
By R. Lanford, E. S. Hildebrandt-Eriksen, A. Petri, R. Persson, M. Lindow, M. E. Munk, Sakari Kauppinen, Henrik Ørum. Science, 2010
775 citations recorded by the source corpus.
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. Targeting a microRNA required for hepatitis C virus infection reduces disease symptoms in chimpanzees. The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)–modified oligonucleotide (SPC3649) complementary to miR-122 leads to long-lasting suppression of HCV viremia, with no evidence of viral resistance or side effects in the treated animals. Furthermore, transcriptome and histological analyses of liver biopsies demonstrated derepression of target mRNAs with miR-122 seed sites, down-regulation of interferon-regulated genes, and improvement of HCV-induced liver pathology. The prolonged virological response to SPC3649 treatment without HCV rebound holds promise of a new antiviral therapy with a high barrier to resistance.
Subfields: Cancer Research, Hepatology, Immunology
View Paper: https://www.semanticscholar.org/paper/3d61988f1d0853214094e60a5d9a4e483e4bbf2f
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In Cancer Research
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In Hepatology
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Citations in the corpus
- The Potential for microRNA Therapeutics and Clinical Research (2019, positive): “Nonhuman primate models have also been successfully incorporated into preclinical miRNA investigations and supported the initiation of clinical trials, such as for the miR-122 repressor, Miravirsen, in the treatment of Hepatitis C Virus (HCV) (Lanford et al., 2010; Janssen et al., 2013). miRNAs AS”
- Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. (2012, positive): “Finally, miR-122 inhibition therapy using an LNA-modified antisense oligonucleotide, SPC3639, is currently in phase II clinical trials for the treatment of HCV infection (5).”
- MicroRNA and cancer (2012, positive): “Studies on the inhibition of endogenous miRNA were pioneered by groups studying the liver-specificmiR-122 and its roles in controlling plasma cholesterol levels and facilitating Hepatitis C virus replication (Elmen et al., 2008a; Krutzfeldt et al., 2005; Lanford et al., 2010).”
- miR-122--a key factor and therapeutic target in liver disease. (2015, positive): “Indeed, the inhibitor reduced HCV RNA levels in the majority of treated animals and its effect was gradually lost once the inhibitor was withdrawn [112], confirming a sustained but reversible inhibition of miR-122 in vivo.”
- MicroRNA Functions in Stress Responses (2010, positive): “Anantagomir againstmiR-122hasbeendemonstrated in animals to lower hepatitis C virus replication levels and cholesterol levels (Elmen et al., 2008; Krutzfeldt et al., 2005; Lanford et al., 2010).”