scholarly journals Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection

Science ◽  
2009 ◽  
Vol 327 (5962) ◽  
pp. 198-201 ◽  
Author(s):  
Robert E. Lanford ◽  
Elisabeth S. Hildebrandt-Eriksen ◽  
Andreas Petri ◽  
Robert Persson ◽  
Morten Lindow ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Locked Nucleic Acid ◽  
Hcv Rna ◽  
Hepatitis C Virus Infection ◽  
Chronic Hepatitis C Virus ◽  
Cultured Liver Cells ◽  
Liver Biopsies ◽  
Rna Accumulation ◽  
Modified Oligonucleotide

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.

scholarly journals Demonstration of Hepatitis C Virus RNA withIn SituHybridization Employing a Locked Nucleic Acid Probe in Humanized Liver of Infected Chimeric Mice and in Needle-Biopsied Human Liver

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Kazuya Shiogama ◽  
Ken-ichi Inada ◽  
Michinori Kohara ◽  
Hidemi Teramoto ◽  
Yasuyoshi Mizutani ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nucleic Acid ◽  
Oligonucleotide Probe ◽  
High Sensitivity ◽  
Locked Nucleic Acid ◽  
Hcv Rna ◽  
Chimeric Mice ◽  
Rt Pcr ◽  
Modified Oligonucleotide

Background.In situhybridization (ISH) with high sensitivity has been requested to demonstrate hepatitis C virus (HCV) RNA in formalin-fixed, paraffin-embedded (FFPE) sections of the liver.Methods. ISH employing a locked-nucleic-acid- (LNA-)modified oligonucleotide probe and biotin-free catalyzed signal amplification system (CSAII) was applied to HCV-RNA detection in the liver tissue. Nested reverse-transcription polymerase chain reaction (RT-PCR) was performed for HCV genotyping using total RNA extracted from FFPE sections. The target tissues included FFPE tissue sections of humanized livers in HCV-infected chimeric mice (HCV genotypes 1a, 1b, and 2a and noninfected) and of needle-biopsied livers from HCV-infected patients.Results. HCV-RNA was demonstrated with the ISH technique in HCV-infected liver tissues from both chimeric mice and 9 (82%) of 11 patients with HCV infection. The HCV signals were sensitive to RNase. Nested RT-PCR confirmed the genotype in 8 (73%) of 11 livers (type 1b: 6 lesions and type 2a: 2 lesions). HCV-RNA was not identified in chronic hepatitis B lesions, fatty liver, autoimmune hepatitis, and hepatocellular carcinoma.Conclusion. ISH using the LNA-modified oligonucleotide probe and CSAII was applicable to detecting HCV-RNA in routinely prepared FFPE liver specimens.

Detection of HCV-RNA in saliva of patients with chronic hepatitis C virus infection

2002 ◽  
Vol 36 ◽  
pp. 103
Author(s):  
Angeles Castro ◽  
Manuel Hermida ◽  
Sandra Barral ◽  
Miguel C. Ferreiro ◽  
Rafael Laredo ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Chronic Hepatitis C ◽  
Hcv Rna ◽  
Hepatitis C Virus Infection ◽  
Chronic Hepatitis C Virus
Sign in / Sign up

Export Citation Format

Share Document