Noncationic Material Design for Nucleic Acid Delivery

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 nonviral delivery vehicles, cationic materials are favored because of their high loading capacity for nucleic acids and prominent cellular uptake efficiency through electrostatic interactions. However, cationic moieties at high dosage tend to induce severe cytotoxicity due to interference with cell membrane integrity. In contrast, noncationic materials present alternative delivery approaches with less safety concerns than cationic materials. In this Progress Report, principles of noncationic material design for nucleic acid delivery are discussed. Examples of such noncationic platforms are highlighted, including complexation or conjugation with nucleic acids and self‐assembled nucleic acid structures.