Rational Design of Immunostimulatory siRNAs

摘要: Short-interfering RNAs (siRNAs) have engendered much enthusiasm for their ability to silence the expression of specific genes. However, it is now well established that siRNAs, depending on sequence, can be variably sensed by innate immune system through recruitment toll-like receptors 7 and 8 (TLR7/8). Here, we aimed identify sequence-based modifications allowing design bifunctional siRNAs with both proinflammatory silencing activities, potentially increased therapeutic benefits. We found introduction a micro-RNA (miRNA)-like nonpairing uridine-bulge in passenger strand robustly immunostimulatory activity human cells. This sequence modification had no effect efficiency siRNA. Increased immunostimulation was cells, conserved required Dicer-substrate scaffold. The cytokine production resulted enhanced protection against Semliki Forest virus (SFV) infection, viral assays. Thus, characterize scaffold applicable any given siRNA results activation without affecting gene silencing. Our data suggest this coupled structural differentially recruits TLR8 over TLR7, could potential application antiviral therapies.