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