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Human papillomavirus type 16 and 18 (HPV16/18) E6 and E7 oncogene DNA represents the genetic material of high-risk HPV strains responsible for the majority of cervical and other anogenital cancers (1, 4). These genes are typically integrated into the host cell genome during persistent infection, where they drive the oncogenic process by encoding the E6 and E7 oncoproteins (3, 11). E6 promotes the ubiquitination and degradation of the tumor suppressor protein p53, while E7 binds to and inactivates the retinoblastoma protein (pRb), leading to the loss of cell cycle control and the prevention of apoptosis (1, 4, 19). As a therapeutic target, the DNA sequences of these oncogenes are utilized in DNA vaccines like VGX-3100 and MEDI0457 to elicit a robust, antigen-specific CD8+ T-cell response against tumor cells (1, 5, 17). Additionally, modern gene-editing technologies such as CRISPR/Cas9 and TALENs are being developed to directly target and disrupt these DNA sequences within the host genome to halt oncoprotein production and induce tumor cell death (1, 6). Targeting the DNA level is a critical strategy for treating established HPV-associated malignancies and precancerous lesions where the virus has already integrated (2, 9). Clinical development of DNA-based therapies often involves electroporation or the use of adjuvants to enhance the relatively weak immunogenicity of plasmid DNA (5, 17). Overall, these oncogenes are the primary drivers of HPV-mediated transformation and remain the most promising targets for therapeutic intervention in HPV-related diseases (1, 11).
DNA vaccines deliver plasmid DNA encoding E6 and E7 to induce a T-cell mediated immune response against infected cells (1, 2, 5); gene-editing tools like CRISPR/Cas9 directly disrupt the viral DNA sequences to halt oncoprotein production and restore tumor suppressor functions (1, 6).
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