Hepatitis B virus genomic RNA (HBV RNA)

Hepatitis B virus (HBV) genomic RNA, primarily the pregenomic RNA (pgRNA), is a central component of the HBV replication cycle. Transcribed from the covalently closed circular DNA (cccDNA) in the host cell nucleus, pgRNA serves as the essential template for reverse transcription into the viral DNA genome and as the messenger RNA for the synthesis of the viral core protein and polymerase (P) (4, 16, 20). In addition to pgRNA, the virus produces several subgenomic mRNAs that encode surface antigens and the X protein (10, 16). Because these transcripts share overlapping sequences and a common 3' polyadenylation signal, they represent a highly efficient target for sequence-specific degradation (1, 3, 11). Therapeutic strategies such as RNA interference (RNAi) and antisense oligonucleotides (ASOs) are designed to bind and degrade these viral RNAs, effectively silencing the production of all viral proteins and halting replication (5, 6, 11). By reducing the burden of viral antigens like HBsAg, which are known to suppress the host's immune response, these therapies aim to restore immune control and achieve a functional cure for chronic hepatitis B (1, 8). Clinical trials have demonstrated that targeting HBV RNA can lead to significant and sustained reductions in viral markers (1, 7). However, challenges remain, including the potential for liver toxicity manifested as ALT flares and the need for effective delivery to hepatocytes (1, 14).

Other names

Pregenomic RNApgRNAHBV transcriptsHBV mRNAHBV pregenome

RNA interference (RNAi) and antisense oligonucleotides (ASO) target and degrade viral RNA transcripts, including pgRNA and subgenomic mRNAs, thereby inhibiting viral protein synthesis and DNA replication (1, 5, 11).