Target intelligence / Profile preview

Hepatitis B virus X protein open reading frame RNA (HBV HBx ORF RNA)

Target
HBV HBx ORF RNA
Molecular classification
Viral RNA, Messenger RNA
01

Overview

The Hepatitis B virus (HBV) HBx open reading frame (ORF) RNA is a critical therapeutic target for the treatment of chronic hepatitis B (CHB). This RNA sequence encodes the HBx protein, a multi-functional transactivator that is essential for the transcription of the viral genome from covalently closed circular DNA (cccDNA) (Source: PubMed, PMID: 26011163). Due to the overlapping nature of the HBV genome, the HBx ORF is present in all viral transcripts, including the pre-genomic RNA (pgRNA) and subgenomic mRNAs (Source: NIH, PMC4664495). Consequently, therapeutic strategies such as RNA interference (RNAi) and antisense oligonucleotides (ASOs) that target this region can effectively degrade all viral RNA species, leading to a profound reduction in the expression of all viral proteins, most notably the Hepatitis B surface antigen (HBsAg) (Source: Journal of Hepatology, DOI: 10.1016/j.jhep.2020.11.030). This broad suppression is intended to alleviate the immune exhaustion caused by high levels of viral antigens, potentially restoring the host's immune response and facilitating a functional cure (Source: Lancet Gastroenterology & Hepatology, DOI: 10.1016/S2468-1253(22)00001-X). The HBx protein also plays a role in the development of hepatocellular carcinoma by modulating host cell signaling and inhibiting DNA repair (Source: Wikipedia, Hepatitis B virus X protein).

Other names
HBV X gene RNAHBx mRNAHepatitis B virus X gene transcriptHBV X-ORF RNA
02

Mechanism of action

RNA interference (RNAi) or antisense oligonucleotide (ASO) mediated degradation of viral transcripts, leading to the reduction of all HBV proteins and pre-genomic RNA.

03

Biological functions

Viral replicationTransactivation of host and viral genesEpigenetic regulation of cccDNAModulation of host cell signaling pathwaysInhibition of apoptosisPromotion of cell cycle progression
04

Disease associations

Chronic Hepatitis BHepatocellular CarcinomaLiver Cirrhosis
05

Safety considerations

ALT flares (immune-mediated)Off-target RNA degradationInjection site reactionsPotential for long-term suppression of host genes if sequence homology exists
06

Interacting drugs

Bepirovirsen (GSK3228836)

4 more in the full profile.

07

Biomarkers

Hepatitis B surface antigen (HBsAg) levelsHBV DNAHepatitis B core-related antigen (HBcrAg)Alanine aminotransferase (ALT)

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