Hepatitis B virus RNA transcripts (S and X genes) (HBV S/X RNA)

Hepatitis B virus (HBV) RNA transcripts from the S and X genes are essential for the viral life cycle and the maintenance of chronic infection (Seeger & Mason, 2000, Microbiology and Molecular Biology Reviews). The S gene transcripts encode the surface antigens (HBsAg), which are produced in vast excess to decoy the host immune system, while the X gene transcript encodes the HBx protein, a transactivator necessary for viral replication and a key factor in the development of hepatocellular carcinoma (Lucifora & Protzer, 2016, Journal of Hepatology). Because the HBV genome is organized into overlapping open reading frames, targeting the S and X regions with antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) allows for the simultaneous degradation of multiple viral RNA species, including the pregenomic RNA (pgRNA) (Wooddell et al., 2017, Science Translational Medicine). This therapeutic strategy, employed by drugs like Bepirovirsen and JNJ-3989, aims to significantly reduce viral protein load, particularly HBsAg, to facilitate the restoration of the host's innate and adaptive immune responses (Yuen et al., 2021, Nature Medicine). Achieving such a reduction is considered a critical step toward a functional cure for chronic hepatitis B, potentially preventing progression to cirrhosis and liver cancer.

Other names

HBV S and X gene transcriptsHepatitis B virus mRNAHBV subgenomic RNAHBV S-ORF and X-ORF transcriptsHBV RNA

Antisense oligonucleotide-mediated RNase H cleavage or RNA interference (RNAi) leading to sequence-specific degradation of viral mRNA and reduction of viral protein production.