The efficacy evaluation of a lung epithelial cell-specific siRNA carrier for the therapy of allergic asthma

Abstract

RNAi come into the spotlight as a potent tool for disease therapy. We used a siRNA (short interfering RNA) carrier that specifically binds to lung epithelial cells and tested its efficiency in vitro and in vivo. ESP-9R peptide as siRNA carrier is comprised of a targeting peptide that binds to the nicotinic acetylcholine receptor expressed on lung epithelial cells with poly-9-arginine, siRNA-complexing moiety. We found that nicotinic acetylcholine receptor exists in mouse lung epithelial cell line (MLE 12 cell) and epithelial cells in mouse lung tissue. ESP-9R peptide effectively delivered siRNA to the lung epithelial cells and induced gene silencing. We also found that administration of siRNA conjugated with ESP-9R to mice remains longer than naked siRNA. To confirm the therapeutic effect of ESP-9R peptide in vivo, we established asthma mouse model and designed siRNAs targeting IL-4Rα. Our data suggest that our peptide can specifically deliver siRNA to the lung epithelial cells and can be a good material of a novel RNAi (RNA interference)-based approach to reducing respiratory inflammation.