Hepatitis B virus messenger RNA encoding Hepatitis B surface antigen (HBV mRNA (HBsAg))

Hepatitis B virus (HBV) messenger RNA encoding the Hepatitis B surface antigen (HBsAg) is a critical intermediate in the viral life cycle, serving as the template for the synthesis of the envelope proteins required for virion assembly and secretion (Liang, 2009, Hepatology). In chronic HBV infection, the overproduction of HBsAg is thought to contribute significantly to immune exhaustion, preventing the host's immune system from clearing the virus (Rehermann & Nascimbeni, 2005, Nature Reviews Immunology). By targeting this specific mRNA sequence, therapeutic agents such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) can silence the expression of HBsAg across all viral transcripts (Wooddell et al., 2020, Molecular Therapy). This reduction in viral protein burden is intended to restore the host's immune response and achieve a functional cure, characterized by sustained HBsAg loss (Yuen et al., 2021, Nature Medicine). Clinical candidates targeting this mRNA, such as Bepirovirsen and JNJ-3989, have shown the ability to significantly reduce serum HBsAg levels in patients with chronic hepatitis B (Gane et al., 2019, The Lancet Infectious Diseases).

Other names

HBV S-mRNAHepatitis B virus surface mRNAHBV pre-S1/pre-S2/S mRNAHBsAg-encoding mRNAHBV 2.1kb and 2.4kb transcripts

Degradation of viral mRNA via RNA interference (RNAi) or antisense oligonucleotide (ASO) pathways to inhibit the translation of HBsAg and other viral proteins (Wooddell et al., 2020, Molecular Therapy).