Hepatitis B virus transcripts encoding hepatitis B surface antigen and HBx protein (HBV HBsAg/HBx mRNA)

Hepatitis B virus (HBV) transcripts encoding the hepatitis B surface antigen (HBsAg) and the HBx protein are critical components of the viral life cycle and key targets for novel antiviral therapies [1]. HBsAg is essential for viral entry and is produced in massive excess by infected hepatocytes, contributing to immune exhaustion and the persistence of chronic infection [2]. The HBx protein is a multifunctional regulator that promotes viral replication and is strongly associated with the development of hepatocellular carcinoma through its interaction with host cell signaling pathways [2]. By targeting these specific mRNA sequences using RNA interference (RNAi) or antisense oligonucleotides (ASOs), researchers aim to silence the production of all viral proteins, thereby reducing the viral load and restoring the host's immune response [3]. This approach is particularly focused on achieving a "functional cure," characterized by the sustained loss of HBsAg from the blood [4]. Clinical candidates like bepirovirsen and various siRNA molecules are currently being evaluated for their ability to degrade these transcripts and improve outcomes for patients with chronic hepatitis B [4, 5]. Sources: [1] Liang TJ, Hepatology 2009; [2] Seeger C & Mason WS, Virology 2015; [3] Yuen MF et al., Lancet Gastroenterol Hepatol 2020; [4] Yuen MF et al., N Engl J Med 2022; [5] Gane E et al., Hepatology 2020.

Other names

HBV mRNAHepatitis B virus messenger RNAHBsAg mRNAHBx mRNAHBV X-region transcriptsHBV S-region transcripts

RNA interference (siRNA) or antisense oligonucleotide (ASO) mediated degradation of viral mRNA, leading to reduced production of HBsAg and HBx proteins.