Gene Therapy Approaches for Treating HPV-Induced Damage in Human Tissues and Cells

Abdullah Bandar Baraka Almutiri, Saad Obaid Alfraidi, Abdallah Ali Hausawi, Mohammed Alsaeed, Fadhel Zaben Alotaibi, Sari S. Sabban, Mohamed Morsi Mohamed Ahmed

Abstract


Human papillomavirus (HPV) is a leading cause of cervical and other anogenital and oropharyngeal cancers, with high-risk HPV types such as HPV-16 and HPV-18 playing a major role in oncogenesis. The viral oncoproteins E6 and E7 interfere with tumor suppressor proteins p53 and retinoblastoma (pRb), leading to uncontrolled cell proliferation, genetic instability, and resistance to apoptosis. While HPV vaccines have significantly reduced infection rates, they do not eliminate pre-existing infections or treat HPV-associated malignancies. This has driven interest in gene therapy as a potential treatment option for HPV-induced cellular damage. Gene therapy approaches, particularly CRISPR-Cas9, have demonstrated efficacy in selectively targeting and disrupting HPV oncogenes, leading to tumor regression. Other gene-editing techniques, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), also show promise in HPV gene disruption. Efficient delivery systems, including viral and non-viral vectors such as nanoparticles, liposomes, and adeno-associated viruses (AAVs), are being optimized to enhance therapeutic outcomes. However, challenges remain, particularly concerning off-target effects, delivery efficiency, and potential immunogenic responses.  This review explores the mechanisms of HPV-induced carcinogenesis, the role of gene therapy in targeting viral oncogenes, and advancements in gene-editing technologies. Future directions include integrating gene therapy with immunotherapy, developing personalized treatment strategies, and improving delivery mechanisms to enhance specificity and safety. While gene therapy holds significant promise for eradicating HPV-driven malignancies, further research is needed to refine these approaches for clinical application.

Keywords:

Oncology, Cancer biology, Molecular biology, Biochemistry, Biotechnology, Genomics

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References


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DOI: https://doi.org/10.62940/als.v13i1.3854

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