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Hepatitis B virus X open reading frame (ORF) mRNA transcripts are the templates for the synthesis of the HBx protein, a multifunctional regulatory protein essential for the HBV life cycle and pathogenesis. The HBx protein acts as a potent transactivator that modulates host cell signal transduction, interferes with DNA repair mechanisms, and alters cell cycle checkpoints, significantly contributing to the development of hepatocellular carcinoma (HCC). Because all HBV mRNA transcripts, including the X transcript, share a common 3' polyadenylation signal, they are highly susceptible to sequence-specific degradation via RNA interference (RNAi) or antisense oligonucleotides (ASOs). Targeting these transcripts aims to reduce the viral protein burden, particularly HBsAg and HBx, to restore the host immune response and achieve a functional cure for chronic hepatitis B infection. Current therapeutic strategies involve small interfering RNAs (siRNAs) and ASOs that specifically bind to conserved regions of the HBV genome to trigger the degradation of these mRNA transcripts.
RNA interference (RNAi) mediated degradation, Antisense oligonucleotide (ASO) mediated RNase H cleavage, and inhibition of translation.
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