The Hepatitis C Virus (HCV) is a member of the Flaviviridae family, characterized by a positive single-stranded RNA genome of approximately 9.6 kilobases. Upon infection of hepatocytes, the viral genome is released into the cytoplasm, where it is translated into a polyprotein. This polyprotein is subsequently cleaved by viral and cellular proteases to produce ten viral proteins, including structural proteins (Core, E1, and E2) and non-structural proteins (P7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) .
Nonstructural protein 3 (NS3), also known as p-70, is a multifunctional enzyme that plays a crucial role in the viral life cycle. It is a 70 kDa cleavage product of the HCV polyprotein and exhibits both serine protease and helicase activities . The serine protease domain of NS3 is responsible for cleaving the viral polyprotein to release other non-structural proteins, which are essential for viral replication. The C-terminal two-thirds of NS3 function as a helicase and nucleoside triphosphatase, facilitating the unwinding of RNA or single-stranded DNA (ssDNA) in a 3’ to 5’ direction .
NS3 is also implicated in the oncogenic processes associated with HCV infection. Research indicates that NS3 contributes to several carcinogenic mechanisms, including proliferative signaling, resistance to cell death, genomic instability, invasion and metastasis, tumor-related inflammation, immune evasion, and replicative immortality. These transformative effects on cells underscore the significance of NS3 in the development of hepatocellular carcinoma (HCC) .
Mouse antibodies, also known as murine antibodies, are immunoglobulins produced by mice in response to antigens. These antibodies can be harvested and used for various research and therapeutic purposes. There are five antibody isotypes in mice, similar to humans: IgA, IgD, IgE, IgG, and IgM. Each isotype has a different heavy chain and serves distinct functions in the immune response .
Monoclonal antibodies (MAbs) are a type of antibody produced by identical immune cells that are clones of a unique parent cell. These antibodies are highly specific to a particular antigen and are widely used in diagnostics, research, and therapy. Historically, mice were extensively used in the production of monoclonal antibodies. However, the use of mouse antibodies in humans can trigger an immune response known as the Human Anti-Mouse Antibody (HAMA) response. This response can range from mild reactions, such as rashes, to severe and life-threatening conditions, such as kidney failure. The HAMA response can also reduce the effectiveness of the treatment and complicate laboratory measurements .
To mitigate these issues, advancements in antibody engineering have led to the development of chimeric and humanized antibodies, which contain a higher proportion of human sequences. These engineered antibodies are less likely to be recognized as foreign by the patient’s immune system, reducing the risk of adverse immune responses. Fully human monoclonal antibodies, produced using in vitro techniques or transgenic mice expressing human antibodies, have further improved the safety and efficacy of antibody-based therapies .