Hepatitis B virus RNA transcripts containing the HBx open reading frame (HBV HBx RNA)

Hepatitis B virus (HBV) RNA transcripts containing the HBx open reading frame (ORF) are critical targets for novel antisense and RNA interference (RNAi) therapies. These transcripts encompass the 0.7 kb X mRNA and the 3' ends of all other HBV transcripts, including the pregenomic RNA (pgRNA), which are co-terminal (Slagle & Bouchard, 2016, Nat Rev Gastroenterol Hepatol). The HBx protein produced from these transcripts is a regulatory protein required for the initiation and maintenance of viral transcription from the cccDNA reservoir (Lucifora et al., 2014, Science). Furthermore, HBx is implicated in hepatocarcinogenesis by disrupting host cell signaling and DNA repair (Levrero & Zucman-Rossi, 2016, J Hepatol). Drugs such as JNJ-3989 and VIR-2218 target this region to induce the degradation of all viral RNA species, effectively reducing the levels of circulating viral antigens like HBsAg (Gane et al., 2020, Lancet Infect Dis). This reduction is a key strategy for achieving a functional cure by potentially restoring the host's immune response against the virus (Yuen et al., 2021, J Hepatol). This target is particularly advantageous because it allows for the silencing of gene products from both episomal cccDNA and integrated HBV DNA sequences.

Other names

HBV X mRNAHBx-containing transcriptsHepatitis B virus X gene transcriptsHBV RNA

RNA interference (RNAi) mediated degradation of viral transcripts and antisense oligonucleotide (ASO) mediated RNase H cleavage, leading to reduced translation of viral proteins (Gane et al., 2020, Lancet Infect Dis; Yuen et al., 2022, NEJM).