| 초록 |
For successful RNA interference (RNAi) therapeutics for neurodegenerative diseases, development of blood brain barrier (BBB) permeable CNS-targeted gene delivery vehicle is an important issue. Here, we report a novel brain-targeted non-viral vector, osmotically active polymanntiol-based gene transporter (PMT) modified with rabies virus glycoprotein (RVG). The synergistic effect in improved BBB permeability of RVG-PMT/siRNA complexes was achieved by targeting ability of RVG ligand and efficient evasion of lysosomal degradation in brain endothelial cells via caveolar endocytosis stimulating effect of PMT. The possible mechanism associated with BBB permeability of RVG-PMT/siRNA complexes was examined using in vitro BBB model. The therapeutic potential of RVG-PMT in Alzheimer’s disease was demonstrated by enhanced efficiency of BACE1 silencing in vitro and in vivo. Our novel brain-targeting gene vehicle, RVG-PMT, represented a promising tool for RNAi therapeutics for neuronal diseases. |
