Hepatitis B virus S gene messenger RNA (HBV S mRNA)

The Hepatitis B virus (HBV) S gene messenger RNA (mRNA) is a vital viral transcript responsible for the synthesis of the hepatitis B surface antigens (HBsAg), which include the small (S), medium (M), and large (L) surface proteins [6, 12]. These proteins are essential for the formation of the viral envelope and the secretion of infectious virions, as well as the production of non-infectious subviral particles that circulate in the blood to overwhelm the host's immune system [12]. Because the HBV genome consists of overlapping open reading frames, the S gene sequence is present in multiple viral transcripts, including the pregenomic RNA (pgRNA) and the 2.4 kb and 2.1 kb mRNAs [12, 17]. Targeting this mRNA with sequence-specific therapeutics like small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) allows for the simultaneous degradation of multiple viral transcripts, effectively silencing HBsAg expression [2, 3]. This reduction in viral antigen load is a key strategy for restoring the host's exhausted T-cell response and achieving a functional cure for chronic hepatitis B [2, 11]. Clinical candidates such as bepirovirsen and various GalNAc-conjugated siRNAs are currently in development to exploit this mechanism [2, 8].

Other names

Hepatitis B virus surface gene mRNAHBsAg mRNA2.1 kb HBV mRNAHBV S transcriptHepatitis B virus S gene mRNA

Drugs targeting this mRNA, such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs), utilize RNA interference or RNase H-mediated cleavage to degrade the transcript, thereby inhibiting the translation of HBsAg and other viral proteins.