Hepatitis B virus pre-genomic RNA and subgenomic mRNAs (HBV pgRNA/sgmRNA)

Hepatitis B virus (HBV) pre-genomic RNA (pgRNA) and subgenomic mRNAs (sgmRNAs) are the primary RNA transcripts produced from the viral covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes (NIH, 2023). The pgRNA is a critical multifunctional intermediate that serves as the template for reverse transcription to generate new viral DNA and as the messenger RNA for the synthesis of the core protein and viral polymerase (NIH, 2024). Subgenomic mRNAs are responsible for the translation of the surface antigens (HBsAg), the X protein (HBx), and the precore protein (HBeAg) (NIH, 2025). These RNA molecules are the targets of emerging therapeutic classes, including RNA interference (RNAi) and antisense oligonucleotides (ASOs), which aim to achieve a functional cure for chronic hepatitis B (ResearchGate, 2024). By degrading these transcripts, these therapies can simultaneously inhibit viral replication and reduce the high levels of circulating viral antigens that contribute to host immune exhaustion (NIH, 2025). Clinical candidates such as bepirovirsen and imdusiran have demonstrated the ability to potently suppress viral markers in clinical trials (NIH, 2025; ResearchGate, 2024). However, therapeutic challenges include the potential for liver toxicity (ALT flares), the need for efficient hepatocyte delivery, and the risk of viral resistance due to sequence mutations (NIH, 2025; MDPI, 2024).

Other names

HBV RNAHBV transcriptsHepatitis B virus pregenomic RNAHepatitis B virus subgenomic mRNAHBV mRNAHBV pgRNAHBV sgmRNA

RNA interference (siRNA) or antisense oligonucleotide (ASO) mediated degradation of viral RNA transcripts, which inhibits the translation of viral proteins (HBsAg, HBeAg, HBcAg, Polymerase, HBx) and removes the template for reverse transcription, thereby suppressing viral replication and antigen production.