Synthetic KL4 peptide as new carrier of siRNA therapeutics for pulmonary delivery

Yingshan Qiu, Michael Y.T. Chow & Jenny K.W. Lam

Small interfering RNA (siRNA) has great potential for the treatment of various respiratory diseases through RNA interference (RNAi), but their clinical application is hindered by the lack of a safe and effective pulmonary delivery system. KL4 peptide is a synthetic amphipathic peptide that was previously developed to mimic the function of pulmonary surfactant protein B (SP-B). Its potential as siRNA carrier for pulmonary delivery was examined in this study. The cationic KL4 peptide was able to bind with siRNA to form complexes at 15:1 ratio (peptide to siRNA weight ratio) or above. It also mediated efficient gene silencing on lung epithelial cells, with 20:1 ratio as the optimal ratio for siRNA transfection. Furthermore, the KL4/siRNA complexes were not toxic at concentrations used for transfection in vitro. The study shows that KL4 peptide appears to be a promising candidate for siRNA delivery. Further investigation on animal study and work on aerosol formulation are required to develop KL4 peptide as siRNA carrier for clinical application.

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