Hepatitis B virus S open reading frame mRNA (HBV S mRNA)

The Hepatitis B virus (HBV) S open reading frame (ORF) mRNA is a vital viral transcript that encodes the three forms of the Hepatitis B surface antigen (HBsAg): Large, Middle, and Small proteins. These proteins are essential components of the viral envelope and are also secreted as non-infectious subviral particles that serve to exhaust the host's immune system, facilitating chronic infection (ViralZone, SIB). By targeting this specific mRNA, novel therapeutics such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) can trigger sequence-specific degradation of the transcript. This process significantly reduces the production of HBsAg, which is a key barrier to achieving a functional cure in patients with chronic hepatitis B (NEJM, 2022). Reducing the burden of viral antigens is hypothesized to allow for the restoration of the host's innate and adaptive immune responses against HBV (PubMed, PMID: 34143766). Clinical candidates like Bepirovirsen and JNJ-3989 have demonstrated the potential of this target to achieve sustained HBsAg loss in clinical trials (GSK, 2023; Arrowhead Pharmaceuticals, 2023).

Other names

Hepatitis B virus surface antigen mRNAHBsAg mRNAHBV S gene transcriptPre-S2/S mRNAHBV S-ORF transcript

Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) target the mRNA sequence to induce its degradation via RNase H or the RNA-induced silencing complex (RISC), respectively, thereby preventing the translation of Hepatitis B surface antigens (HBsAg) (PubMed, PMID: 36351257).