Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63108, USA.
Biomaterials. 2010 Apr;31(11):3079-86. doi: 10.1016/j.biomaterials.2010.01.006. Epub 2010 Jan 25.
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.
RNA 干扰 (RNAi) 是一种有用的体外研究工具，但将其作为一种安全有效的治疗剂应用，可能需要更好地了解外源性 siRNA 递呈的机制，包括细胞转运和分拣模式。我们报告了一种用于 siRNA 递呈的转染试剂的开发，该试剂采用一种独特的非消化性颗粒-细胞膜相互作用模式，通过形成半融合复合物，导致脂质筏将货物转运到细胞质，绕过通常的内体纳米颗粒摄取途径。我们进一步证明，与传统的转染试剂相比，该试剂在抑制上调的血管黏附分子在内皮细胞中的表达方面具有显著增强的功效。
