Delivery of Preassembled Double-stranded Short Interference RNA-argonaute Protein Complexes for Enhanced RNAi-based Therapeutics


Increasing the efficiency of knockdown using siRNA or miRNA has the potential to boost RNAi technology’s performance in the clinic.

Problem Addressed

Delivering sufficient amount of siRNA or miRNA to achieve efficient knockdown is a challenge in RNAi therapy. Thus, there is a need to increase the efficiency of knockdown per molecule delivered. The current invention delivers preassembled siRNA or miRNA with argonaute protein (Ago2) to enhance knockdown efficiency.


Ago2 is a core component of RISC complex that executes the actual silencing step of RNAi. The current invention preassembles siRNA or miRNA with Ago2 and demonstrates that transfection of preassembled complexes has a higher knockdown efficiency at the same concentration compared to siRNA or miRNA alone. This effect is as high as 3 fold and increases as the molar ratio of Ago2 to siRNA/miRNA gets closer to 1:1.


  • Preassembled siRNA or miRNA with Ago2 protein increases knockdown efficiency by as much as 3 fold