Hepatitis B virus pregenomic and precore messenger RNA (HBV pgRNA/pre-C mRNA)

Hepatitis B virus (HBV) pregenomic RNA (pgRNA) and precore mRNA are the primary 3.5 kb transcripts derived from the viral covalently closed circular DNA (cccDNA) template in the nucleus of infected hepatocytes [1, 10]. The pgRNA is a multifunctional molecule that serves as the essential template for reverse transcription to synthesize the viral DNA genome and as the messenger RNA for the translation of the viral core protein (HBcAg) and polymerase [8, 16, 19]. The precore mRNA, which contains a short 5' extension relative to pgRNA, encodes the precore protein that is post-translationally processed and secreted as the Hepatitis B e antigen (HBeAg) [8, 18]. These transcripts are central to the HBV life cycle and the maintenance of chronic infection, making them high-priority targets for gene-silencing modalities such as RNA interference (RNAi) and antisense oligonucleotides (ASOs) [2, 7, 9]. By facilitating the degradation of these viral RNAs, these therapeutic approaches aim to significantly reduce the viral antigenic burden and replication, potentially enabling the restoration of the host immune response and achieving a functional cure for chronic hepatitis B [3, 6, 14].

Other names

Pregenomic RNApgRNAPrecore mRNApre-C mRNAHBV 3.5 kb RNAHBV 3.5 kb transcriptsHepatitis B virus 3.5 kb mRNA

RNA interference (RNAi) and antisense oligonucleotide (ASO) mediated degradation of viral transcripts, leading to reduced viral replication and antigen production [2, 7, 9]. Additionally, small molecules may inhibit RNA stabilization by targeting host factors like TENT4 [11, 19].