Author: Qiu, Yingshan; Lam, Jenny K. W.; Leung, Susan W. S.; Liang, Wanling
Title: Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside Document date: 2016_9_20
ID: 04pp3lv0_24
Snippet: Compared to viral vectors, non-viral vectors generally have better safety profile and lower production cost. They have been investigated for the pulmonary delivery of the RNAi molecules. Lipid-based, polymer-based and peptide-based are three major non-viral delivery systems [73] . The lipid-based vectors are the most commonly used vectors for RNAi delivery. They include cationic liposomes, solid lipid nanoparticles, solid nanostructured lipid car.....
Document: Compared to viral vectors, non-viral vectors generally have better safety profile and lower production cost. They have been investigated for the pulmonary delivery of the RNAi molecules. Lipid-based, polymer-based and peptide-based are three major non-viral delivery systems [73] . The lipid-based vectors are the most commonly used vectors for RNAi delivery. They include cationic liposomes, solid lipid nanoparticles, solid nanostructured lipid carriers, lipidoids and pH-responsive lipids [74] . Many commercially available transfection agents (i.e., Lipofectamine, Oligofectamine, TransIT-TKO and DharmaFECT) are lipid-based systems [75] [76] [77] [78] . Despite the promising transfection efficacy, the major challenges of using the lipids are the immune response and cytotoxicity [79] . In addition to the lipids, biocompatible and biodegradable natural polymers such as chitosan and dextran, as well as synthetic polymers such as poly lactic-co-glycolic acid (PLGA), polyethylenimine (PEI) and PAMAM dendrimer are used for the preparation of polymeric nanoparticles for RNA delivery [80] [81] [82] [83] [84] [85] . The polymers have relatively low toxicity compared to the lipid-based vectors and are more versatile for chemical modification. For peptide-based delivery systems, peptides such poly(L-lysine) (PLL), cell penetrating peptides (CPPs) and pH-responsive peptides have been investigated for the delivery of the RNAi molecules [86] [87] [88] [89] [90] . Different types of peptides mediate cellular transfection via different mechanisms such as facilitating cellular uptake and promoting endosomal escape. Peptides can be used to carry the RNAi molecules alone or act as a functional component in other carriers. Currently, efficient peptides with low toxicity and high transfection efficacy are still under development. It is noted that for pulmonary delivery, the reduced nuclease activity in the lungs makes successful delivery of unmodified naked RNA become possible [91, 92] . However, the mechanism of how naked siRNA could overcome the extracellular and intracellular barrier following pulmonary administration still remains to be understood.
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