Efficient and safe small RNA delivery to macrophage using peptide‐based nanocomplex

Abstract As one of the gene therapies, RNA interference (RNAi) effectively suppresses only specific genes, targeting various diseases in which they are involved. For the successful process of RNAi, efficient and safe delivery of small RNAs, including small interfering RNA and short hairpin RNA, is essential. Herein, an S‐R11 fusion peptide, SPACE peptide conjugated with poly‐arginine, was introduced to deliver small RNAs into immune cells that are difficult to transfect. This S‐R11 peptide stably formed a spontaneous self‐assembling nanocomplex through electrostatic attraction and hydrogen bonding with small RNAs. The nanocomplex showed about 5.3‐fold better permeation efficiency than the conventional Lipofectamine™ 2000 for RAW 264.7 macrophage cells. Moreover, it induced about 66.2% silencing effect of the target gene in the cells activated with polyinosinic:polycytidylic acid (poly (I:C)). In addition, the cell viability of fusion peptide was ensured even in a concentration range exceeding the concentration used in the nanocomplex. Based on these results, it is expected that the nanocomplex in this study can be used as a new gene delivery system that can overcome the challenge of gene therapies to immune cells.