Supramolecular self-assembled nanoparticles mediate oral delivery of therapeutic TNF-α siRNA against systemic inflammation.
2013
Intervention of the inflammation cascade with tumor necrosis factor-α (TNF-α) monoclonal antibodies or receptors represents a major approach in clinical immunotherapy against inflammatory diseases, which however, often suffers from high cost, autoimmunity to antibodies, and various side effects.[1] siRNA-mediated RNA interference (RNAi) has recently emerged as a potent modality in regulating gene expression by suppressing mRNA translation;[2-13] its high efficiency and specificity has made it a promising treatment paradigm for TNF-α-mediated inflammatory disorders.[14-18] The therapeutic potential of siRNA was recently exemplified by a report of attenuating systemic inflammation by targeting orally delivered Map4k4 siRNA to gut-associated macrophages (GAMs).[19] Owing to the infiltration of GAMs to systemic reticuloendothelial tissues, Map4k4 siRNA-mediated TNF-α knockdown in GAMs extended to other tissues and thus induced systemic anti-inflammatory effects.[19]
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