An LNP-mRNA Delivered Surface Display System Targeting HPV E6/E7 for Immune-Mediated Clearance of Infected Cells: A Theoretical Framework

Current therapeutic approaches for HPV-related lesions primarily rely on activating the immune system through vaccines or treating visible lesions through physical ablation. However, these strategies face limitations including dependence on functional T cells, slow onset of action, and susceptibility to HPV immune evasion. This paper proposes a simplified strategy for directly marking HPV-infected cells for immune-mediated clearance. The approach uses lipid nanoparticles (LNPs) to deliver mRNA encoding an engineered combat protein. After local application, epithelial cells internalize the LNPs, and the mRNA is translated into the combat protein in the cytoplasm. The combat protein contains an AI-designed recognition domain targeting the HPV E6 or E7 oncoprotein, a transmembrane domain, and a highly immunogenic artificial antigen. Upon binding to E6 or E7, the combat protein undergoes a conformational change that exposes the transmembrane domain and the artificial antigen, anchoring the complex to the cell membrane. The displayed artificial antigen is then recognized by cytotoxic T lymphocytes (CTLs), leading to targeted apoptosis of the infected cell. A PEST sequence is included to ensure that unbound combat protein is degraded over time. This approach does not depend on MHC-I presentation of natural viral antigens, thereby bypassing HPV-mediated immune evasion. Because E6 and E7 are continuously expressed in infected cells and HPV has no latent reservoir, the system provides a persistent target for immune recognition. This paper discusses the design logic, operational workflow, feasibility, and validation pathways of this strategy.