Effective gene silencing effect mediated by the KL4/siRNA complexes in lung epithelial cells through clathrin-dependent endocytosis
Yingshan Qiu, Michael Y.T. Chow & Jenny K.W. Lam
Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong
Summary:
Small interfering RNA (siRNA) have been widely investigated for the treatment of various respiratory diseases. A vector with good safety and high efficacy for pulmonary siRNA delivery is a major problem that needs to be addressed. The synthetic peptide KL4 is a 21-residue peptide containing hydrophobic leucine interspersed with cationic lysine, which was designed to mimic the function of surfactant protein B (SP-B). Previous result showed that the KL4/siRNA complexes can successfully induce gene silencing in lung epithelial cells. The aim of this study was to further study the uptake profile of the KL4/siRNA complexes, in order to optimize the system for pulmonary delivery. The result showed that clathrin-mediated endocytosis was involved in cellular uptake of KL4/siRNA complexes. Future study will focus on the in vivo transfection through intratracheal delivery of the complexes.