Design and testing of dual-targeting RNAi compounds. (A) Dual targeting RNAi compound structure: A bulge-containing duplex is formed by two oligos, each containing 19 nt targeting for two different genes. The 3′ portions serve as adaptors to allow formation of the imperfect (containing internal bulge) duplex reminiscent of the homodimer soloRNA shown in Figure 1A. The guide portions for SOD1 (blue) and PPIB (red) are highlighted. (B) Dose response of dual targeting RNAi compounds: SOD1 (blue) or PPIB (red). HEK293 cells were transfected with varying concentrations of the RNAi construct, and gene silencing was measured 24 h post-transfection in reference to the housekeeping gene (HKG; MAP4K4, in this case).
