RNA interference (RNAi) is a useful in vitro research tool, but its application as a safe and effective
therapeutic agent may benefit from improved understanding of mechanisms of exogenous siRNA
delivery, including cell trafficking and sorting patterns. We report the development of a transfection
reagent for siRNA delivery which employs a distinctive non-digestive mode of particle-cell membrane
interaction through the formation of a hemifusion complex resulting in lipid raft transport of cargo to the
cytosol, bypassing the usual endosomal nanoparticle uptake pathway.We further demonstrate markedly
enhanced efficacy over conventional transfection agents for suppressing endothelial cell expression of
upregulated vascular adhesion molecules.
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