Harnessing HPV Virus-like Nanoparticles for Efficient Circular RNA Delivery

Circular RNA (circRNA) has emerged as a promising class of therapeutics and mRNA vaccines. While possessing greater stability and functionality akin to linear mRNA, circRNA still necessitates an efficient and adaptable delivery system to surmount the primary challenge of cellular uptake and membrane penetration. Inspired by the high invasiveness of the virus, in this study, the virus-like nanoparticles (VLNPs) of human papillomavirus (HPV) have been constructed as robust carriers for circRNA encapsulation and transfer through their coassembly monitoring. Notably, the functionalization of a transmembrane peptide (L17E) on the outer surface of VLNPs has led to the development of a more efficient nanocarrier, which has significantly enhanced both the transmembrane delivery and endosomal escape of circRNA. Validation studies employing VLNPs-L17E-packaged circRNA across various cell types have demonstrated notable improvements in target protein expression, ranging from 1.48- to 2.04-fold. These findings underscore the potential of HPV-VLNPs-L17E as a carrier for circRNA delivery, offering promising prospects for RNA therapy applications in the future.