Target intelligence / Profile preview

Hepatitis C virus genomic RNA (HCV RNA)

Target
HCV RNA
Molecular classification
Viral RNA [13], Nucleic acid [9]
01

Overview

Hepatitis C virus (HCV) genomic RNA is a positive-sense, single-stranded RNA molecule approximately 9.6 kilobases in length that serves as the essential genetic blueprint for the virus [13, 18]. It contains a single open reading frame encoding a polyprotein, flanked by highly structured 5' and 3' untranslated regions (UTRs) that coordinate viral translation and replication [15, 17]. The 5' UTR features an internal ribosome entry site (IRES) for cap-independent translation, while the 3' UTR and internal cis-acting replication elements are vital for RNA-dependent RNA synthesis [20, 21]. A distinctive aspect of HCV RNA biology is its reliance on the host liver-specific microRNA, miR-122, which binds to the 5' UTR to stabilize the genome and protect it from host exonucleases [2, 6]. In clinical disease, the persistence of HCV RNA in hepatocytes leads to chronic inflammation, cirrhosis, and an increased risk of hepatocellular carcinoma [10, 17]. Therapeutic strategies targeting the RNA include antisense oligonucleotides like Miravirsen and RG-101, which sequester miR-122 to disrupt viral stability, as well as experimental siRNAs and small molecules designed to interfere with conserved RNA structures [3, 7, 14].

Other names
HCV genome [13]HCV plus-strand RNA [13]Hepatitis C virus RNA [10]HCV (+) RNA [18]
02

Mechanism of action

Inhibition of viral translation and replication through sequestration of host factors (e.g., miR-122), RNA interference (siRNA), or lethal mutagenesis via nucleoside incorporation [1, 6, 9, 14].

03

Biological functions

Viral translation [18, 20]Viral replication [17, 21]Viral assembly [18, 22]Innate immune evasion [19]
04

Disease associations

Hepatitis C [13]Liver cirrhosis [17]Hepatocellular carcinoma [17]
05

Safety considerations

Viral resistance due to RNA mutations [2, 6]Hepatotoxicity [10]Potential oncogenic risk from miR-122 inhibition [17]Delivery challenges for oligonucleotides [4, 12]
06

Interacting drugs

Miravirsen (SPC3649) [1, 6]

3 more in the full profile.

07

Biomarkers

HCV RNA viral load [10, 11]HCV genotype [13, 17]Sustained Virological Response (SVR) [10]

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