A Novel Approach in Construction of HPV16 Virus-like Particles with Applications in HPV Related Therapy and Nanotechnology

HPV is part of the papillomavirus family, they infect a large range of animal hosts and account for 5% of human cancers including cervical, anogenital, and oropharyngeal. Over 95% of cervical cancers are caused by HPV16 and HPV18, where HPV16 accounts for 55% of cervical cancers and over 30% of oropharyngeal cancers. There is currently no anti-viral treatment for HPV infection. The standard treatment for HPV caused preinvasive or early invasive cervical cancers is direct removal of affected cells through surgery and radiation. More advanced cases use chemotherapies, immunotherapies, and combinations of them. There are currently three prophylactic vaccines against HPV (Gaurdasil, Gaurdasil-9, and Cervarix) that use L1 containing virus-like particles to induce protection. Vaccination adherence and regular testing varies by geographical region and socioeconomic status, causing continued widespread cases of the disease and more severe cases at time of diagnosis, with concurrent higher mortality. Many research groups are investigating nanomaterials and viral capsids as methods of drug and gene delivery. Accordingly, high throughput methods for nanoparticle and viral characterization are advancing with newer technologies. Modified HPV capsids are showing promising results in cell specific targeting and improved package delivery into target cell with lower, off target cytotoxicity. In this study, HPV16 structural proteins, L1 and L2, were fused to each half of the fluorophore Venus with a specially designed linker that does not constrain capsid assembly and reduces the aggregation point of virus-like particles (VLPs) produced from current methods. The lack of aggregation increases yield by quantity and quality while the linked fluorophore shows promise for applications in high throughput fluorescent activated cell sorting and flow virometry when the technology becomes more widely accessible.

Embargo status: Restricted until 09/2024. To request the author grant access, click on the PDF link to the left.