Adenoviral vaccines have been at the front line in the fight against pandemics caused by viral infections such as Ebola and the coronavirus disease 2019. This has revived an interest in developing these vectors as vaccines and therapies against other viruses of health importance such as hepatitis B virus (HBV). Current hepatitis B therapies are not curative; hence, chronic hepatitis B remains the major risk factor for development of liver disease and death in HBV-infected individuals.
View Article and Find Full Text PDFAvailable treatment for chronic hepatitis B virus (HBV) infection offers modest functional curative efficacy. The viral replicative intermediate comprising covalently closed circular DNA (cccDNA) is responsible for persistent chronic HBV infection. Hence, current efforts have focused on developing therapies that disable cccDNA.
View Article and Find Full Text PDFThe paucity of animal models that simulate the replication of the hepatitis B virus (HBV) is an impediment to advancing new anti-viral treatments. The work reported here employed recombinant adeno-associated viruses (AAVs) to model HBV subgenotype A1 and subgenotype D3 replication in vitro and in vivo. Infection with subgenotype A1 is endemic to parts of sub-Saharan Africa, and it is associated with a high risk of hepatocellular carcinoma.
View Article and Find Full Text PDFExpert Opin Ther Targets
June 2021
: Current therapy for infection with hepatitis B virus (HBV) rarely clears the virus, and viremia commonly resurges following treatment withdrawal. To prevent serious complications of the infection, research has been aimed at identifying new viral and host targets that can be exploited to inactivate HBV replication.: This paper reviews the use of these new molecular targets to advance anti-HBV therapy.
View Article and Find Full Text PDFJ Hepatocell Carcinoma
January 2021
Chronic hepatitis B, a liver disease resulting from persisting hepatitis B virus (HBV) infection, remains a global health challenge despite the availability of an effective vaccine. Various preclinical studies using adeno-associated viruses (AAVs) to deliver anti-HBV RNA interference (RNAi) activators to mediate long-lasting HBV silencing show promise. Recent positive outcomes observed in clinical trials and the FDA approval of AAV-based drugs further demonstrate the potential of AAVs in antiviral therapeutic development.
View Article and Find Full Text PDFChronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants.
View Article and Find Full Text PDFExpert Opin Biol Ther
April 2018
Introduction: Exposure to toxins from the portal circulation, viral infection and by-products of metabolic activity make liver tissue prone to injury. When sustained, associated inflammation leads to activation of hepatic stellate cells (HSCs), deposition of extracellular matrix (ECM) proteins and complicating hepatic fibrosis.
Areas Covered: In this article, the authors discuss utility of therapeutic gene silencing to disable key steps of hepatic fibrogenesis.
Management of infection with hepatitis B virus (HBV) remains a global health problem. Persistence of stable covalently closed circular DNA (cccDNA) during HBV replication is responsible for modest curative efficacy of currently licensed drugs. Novel gene editing technologies, such as those based on CRISPR/Cas9, provide the means for permanently disabling cccDNA.
View Article and Find Full Text PDFChronic infection with hepatitis B virus (HBV) remains a problem of global significance and improving available treatment is important to prevent life-threatening complications arising in persistently infected individuals. HBV is susceptible to silencing by exogenous artificial intermediates of the RNA interference (RNAi) pathway. However, toxicity of Pol III cassettes and short duration of silencing by effectors of the RNAi pathway may limit anti-HBV therapeutic utility.
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