Hepatitis B virus X open reading frame RNA transcripts (HBV X RNA)

Hepatitis B virus (HBV) X open reading frame (ORF) RNA transcripts are essential components of the viral life cycle, serving as the template for the synthesis of the HBx protein. The HBx protein is a potent transactivator that modulates host cell signaling pathways and is required for the transcription of the viral covalently closed circular DNA (cccDNA) (PMID: 26962741). Due to the overlapping nature of the HBV genome, the X ORF sequence is contained within all major viral RNA species, including the pregenomic RNA (pgRNA) and subgenomic mRNAs (PMID: 31534001). This unique genomic structure makes the X ORF RNA an ideal target for sequence-specific therapeutics such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs). By inducing the degradation of these transcripts, these therapies can simultaneously reduce the levels of all HBV proteins, including the surface antigen (HBsAg), which is a major driver of immune exhaustion in chronic hepatitis B (PMID: 33053377). Consequently, targeting the X ORF RNA is a primary strategy in current clinical efforts to achieve a functional cure for chronic HBV infection.

Other names

HBx mRNAHBV X-gene transcriptsHepatitis B virus X protein mRNAHBV X-ORF RNA

Degradation of viral RNA transcripts via RNA interference (RNAi) or antisense oligonucleotide (ASO) mediated RNase H cleavage, thereby preventing the translation of viral proteins and reducing the viral load.