Hepatitis B virus covalently closed circular DNA-derived viral transcript (HBV cccDNA transcript) (HBV cccDNA transcript)

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA)-derived viral transcript refers to the RNA molecules synthesized from the persistent cccDNA reservoir within the nucleus of infected hepatocytes (Martinez et al., 2020, Journal of Hepatology). These transcripts include the pregenomic RNA (pgRNA), which acts as the template for viral DNA replication via reverse transcription, and various subgenomic messenger RNAs (mRNAs) that encode essential viral proteins such as the surface antigen (HBsAg), core protein (HBcAg), and polymerase (Fanning et al., 2019, Nature Reviews Gastroenterology & Hepatology). While standard nucleos(t)ide analog therapies effectively suppress DNA replication, they do not eliminate cccDNA or the production of these viral transcripts, which contribute to the persistence of the infection and the suppression of the host immune system (Gane et al., 2023, The Lancet). Consequently, these transcripts have become a primary target for novel therapeutic interventions, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) (Yuen et al., 2021, The Lancet Gastroenterology & Hepatology). By binding to and promoting the degradation of HBV RNA, these drugs aim to reduce the viral protein burden and inhibit the viral lifecycle, potentially leading to a functional cure for chronic hepatitis B (Lok et al., 2022, Hepatology).

Other names

HBV RNAHBV mRNAHBV pregenomic RNApgRNAHBV viral RNA

RNA interference (RNAi) or antisense oligonucleotide (ASO) mediated degradation of viral RNA transcripts to inhibit protein synthesis and viral replication.