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Simultaneous targeting of three human papillomavirus type 16 oncoproteins using gene editing in a C57BL/6 mouse model of C3 epithelial tumor
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Ali Anvar1    , Azam Bolhassani2 , Iman Salahshoorifar1 , Shiva Irani1 |
1- Faculty of Converging Sciences and Technologies, Science and Research Branch, Islamic Azad University, Tehran, Iran
2- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran , azam.bolhassani@yahoo.com |
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Abstract: (5 Views) |
Background: Human papillomavirus type 16 (HPV16) is a leading cause of cervical cancer, with its oncoproteins E5, E6, and E7 playing pivotal roles in tumor development. This study aimed to investigate the effect of simultaneous targeting of these three oncogenes using CRISPR/Cas9 technology delivered via the HR9 peptide in a mouse model of solid epithelial tumors.
Materials and methods: Female C57BL/6 mice (4–6 weeks old, weighing approximately 15–20 g) were divided into five groups. Subcutaneous injection of HPV16-positive C3 tumor cells was performed. After tumor formation, intratumoral administration of PX460-based CRISPR/Cas9 vectors containing E5, E6, or E7 sgRNAs, complexed with HR9 peptide, was carried out on days 7, 14, and 21. On day 60, apoptosis was assessed using H&E staining, immunohistochemistry (IHC), and caspase-3 expression analysis.
Results: Mice treated with E6-PX460 + E7-PX460 nanoparticles exhibited a statistically significant reduction in tumor size and an increased rate of apoptosis compared to those treated with the triple combination (E5+E6+E7-PX460) or E5-PX460 alone (p<0.0001). These findings indicate the superior therapeutic efficacy of dual targeting of E6 and E7.
Conclusion: Simultaneous targeting of E6 and E7 oncogenes using CRISPR/Cas9 technology delivered via the HR9 peptide effectively induced apoptosis and suppressed tumor growth in C57BL/6 mice. This approach shows promise as a novel targeted strategy for HPV16-related tumor therapy and warrants further investigation.
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| Keywords: HPV16, Oncoproteins, CRISPR/Cas9, Gene editing, C3 tumor cells |
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Subject:
Genetic
Received: 2025/02/4 | Accepted: 2025/06/9 | Published: 2025/12/1
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