Nucleic acid delivery provides effective options to control intracellular gene expression and protein production. Efficient delivery of nucleic acid typically requires delivery vehicles to facilitate the entry of nucleic acid into cells. Among non-viral delivery vehicles, cationic materials are favored because of their high loading capacity of nucleic acids and prominent cellular uptake efficiency through electrostatic interaction. However, cationic moieties at high dosage tend to induce severe cytotoxicity due to the interference on cell membrane integrity. In contrast, non-cationic materials present alternative delivery approaches with less safety concerns than cationic materials. In this Progress Report, principles of non-cationic material design for nucleic acid delivery are discussed. Examples of such non-cationic platforms are highlighted, including complexation or conjugation with nucleic acids and self-assembled nucleic acid structures.
Keywords: Nucleic acid delivery; material design; non-cationic; non-viral.