Dimeric Human β-Defensin 3 as a Universal Platform for Intracellular Delivery of Nucleic Acid Cargos

Abstract

Functional nucleic acids including siRNA, mRNA, and plasmid DNA are promising bioactive molecules to regulate cellular functions uncontrollable by conventional small molecule regulators. To realize successful cellular applications of these nucleic acids, an intracellular gene delivery vehicle with high efficiency and low cytotoxicity is required. Here, we report the dimerization of human β-defensin 3 (DhBD3) promoted by the interaction between β-strands and the application of DhBD3 for efficient delivery of various nucleic acid cargos. DhBD3 with multiple cationic residues could be complexed with various types of polyanionic DNA and RNA. DhBD3 could intracellularly deliver both small and large nucleic acid cargos loaded by complexation to regulate the expression level of target proteins, showing its potential as a universal platform for nucleic acid delivery. In addition, as DhBD3 is a human-derived material with high biocompatibility and can be robustly prepared by an inexpensive method, it is a promisin...