Virus-inspired nucleic acid delivery system: Linking virus and viral mimicry

Targeted delivery of nucleic acids into disease sites of human body has been attempted for decades, but both viral and non-viral vectors are yet to meet our expectations. Safety concerns and low delivery efficiency are the main limitations of viral and non-viral vectors, respectively. The structure of viruses is both ordered and dynamic, and is believed to be the key for effective transfection. Detailed understanding of the physical properties of viruses, their interaction with cellular components, and responses towards cellular environments leading to transfection would inspire the development of safe and effective non-viral vectors. To this goal, this review systematically summarizes distinctive features of viruses that are implied for efficient nucleic acid delivery but not yet fully explored in current non-viral vectors. The assembly and disassembly of viral structures, presentation of viral ligands, and the subcellular targeting of viruses are emphasized. Moreover, we describe the current development of cationic material-based viral mimicry (CVM) and structural viral mimicry (SVM) in these aspects. In light of the discrepancy, we identify future opportunities for rational design of viral mimics for the efficient delivery of DNA and RNA.