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Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are highly prevalent viruses estimated to infect millions of people worldwide and cause significant hepatic disease, including cirrhosis, fulminant hepatitis, and hepatocellular carcinoma. HDV is a defective virus that can propagate only in the presence of HBV. Concurrent infection with HBV and HDV can result in more severe disease outcomes than infection with HBV alone. Thus, there is a need to develop representative animal models to understand these viruses and the immune responses they generate to enhance disease management.
Utilizing AAV vectors, particularly serotype 8 (AAV8) known for its robust hepatotropic properties, has emerged as a potent approach. Creative Biogene's AAV platform, led by experienced scientists, offers AAV particles containing HBV / HDV genome DNA. This facilitates efficient, long-term gene expression, enabling the development of mouse models for sustained HBV / HDV infection. The provided AAV-HBV and AAV-HDV particles support extended transduction, rapid HBV / HDV modeling, and stable expression of hepatitis B / D antigens, serving as a valuable resource for investigating novel targets and treatment approaches in chronic HBV / HDV infection research.
Long-Term and Efficient HBV / HDV Gene Expression: Ensures prolonged and effective expression and replication of HBV / HDV genes in mouse hepatocytes.
Incorporation of Diverse HBV Genotypes: Comprehensive coverage with inclusion of key HBV genotypes enhances versatility and applicability.
Tailored Recombinant AAV Production: Customized capabilities for the production of recombinant AAV, allowing for personalized and specific applications.
The HBV AAV vectors integrate full or partial HBV genomes into AAV capsids using liver-specific promoters, exhibiting high hepatocyte tropism. Systemic or intrahepatic injection ensures liver transduction, enabling HBV gene delivery and establishing chronic infection in mice. This approach efficiently models human disease aspects, including viremia, T cell dysfunction, and liver pathology. Utilizing AAV overcomes challenges associated with traditional hydrodynamic injection, providing consistent results. These AAV tools expedite preclinical testing of antiviral drugs, immunotherapy, and gene editing strategies, accurately recapitulating the intrahepatic HBV lifecycle. Creative Biogene's HBV AAVs facilitate comprehensive studies on chronic hepatitis B pathogenesis and innovative therapy evaluation.
Our products contain the surface antigen genes, and their applications include:
Case Study 1
The precise mechanism by which many virus-based vectors activate immune responses remains unknown. Dendritic cells (DCs), crucial in priming T cell responses and controlling virus replication, play a key role in understanding immune responses triggered by viral vectors. In the research, using VSV (vesicular stomatitis virus) and VLV (VSV-derived lentiviral vectors), diverse dendritic cell activation patterns are unveiled, emphasizing distinct roles in immune response activation post-immunization. Mice vaccinated with VLV, UV-VLV, VSV, or UV-VSV and challenged with AAV-HBV showed that only UV-inactivated VLV, similar to live VLV, protected against AAV-HBV and induced HBV-specific CD8 T cells. This demonstrates that UV-VLV activates antiviral immunity without viral replication when delivered by AAV.
Figure 1. Researchers utilized adeno-associated virus (AAV) serotype 8, encoding a 1.2-mer HBV genome. In male C57BL/6 mice, HBV replication was initiated through intravenous injection of 3×1010 genome copies of AAV-HBV. (Chiale C, et al., 2021).
Case Study 2
HDV (Hepatitis Delta Virus) infection leads to the most severe form of human viral hepatitis. In this study, researchers utilized AAVs to deliver Hepatitis B Virus (HBV) and HDV genomes (HDVg) and antigens to mouse hepatocytes, resulting in liver inflammation, damage, and cell death. Analysis revealed activated lymphocytes and macrophages, but depletion studies ruled them out as responsible for the damage. Transcriptomics indicated interferons and Tumor Necrosis Factor-alpha (TNF-α) as potential culprits. While interferon signaling was not involved, blocking TNF-α reduced injury. Interestingly, AAV delivery of HDAg alone caused severe liver damage independently of T cells and TNF-α. This AAV-mediated HBV/HDV coinfection model sheds light on both immune-mediated and direct viral cytotoxicity in understanding human hepatitis pathogenesis.
Figure 2. AAV-HBV/HDV caused significantly more hepatocyte caspase-3 activation and death than AAV-HBV alone, correlating with aminotransferase levels. Almost all caspase-3 positive cells expressed HDAg, linking HDV to hepatocyte apoptosis. (Usai C, et al., 2020).
Q: What are HBV genome AAV particles?
A: HBV genome AAV particles are engineered vectors designed for the delivery of the hepatitis B virus genome.
Q: How are they engineered to facilitate HBV gene delivery?
A: They involve the incorporation of either full or partial HBV genomes into AAV capsids, utilizing liver-specific promoters such as AAV8 to achieve a high level of hepatocyte tropism.
Q: What is the scope of application for HBV AAV particles?
A: Their applications encompass the efficient expression and replication of HBV genes in mice, mimicking human disease features like viral viremia, T cell dysfunction, and liver pathology.
Q: Why choose AAV over traditional DNA delivery methods?
A: AAV overcomes challenges associated with traditional hydrodynamic injection, providing more consistent results, particularly in the delivery of HBV genes.
Q: What role do HBV AAV tools play in preclinical models?
A: These tools expedite preliminary testing of antiviral drugs, immunotherapy, and gene editing strategies, accurately reproducing the intrahepatic HBV lifecycle and facilitating in-depth studies of the pathogenesis of chronic hepatitis B and the evaluation of innovative therapeutic approaches.
| Cat.No. | Product Name | Price |
|---|---|---|
| AAVH001Z | HBV-D/ayw AAV (Serotype 8) | Inquiry |
| AAVH002Z | HBV-C/adr AAV (Serotype 8) | Inquiry |
| AAVH003Z | HBV-C/RD AAV (Serotype 8) | Inquiry |
| AAVH004Z | HBV-B/adw AAV (Serotype 8) | Inquiry |
| AAVH005Z | hAAT-HDV-I AAV (Serotype 8) | Inquiry |
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