FIGURE 2.

Rational design of highly efficient, artificial miRNA/miRNA* duplexes. (A) A conventional siRNA. (B) A functionally asymmetric siRNA duplex is designed by introducing a mismatch at the 5′-end of the guide strand (pink). (C) An artificial miRNA/miRNA* duplex is designed from the asymmetric siRNA in B by appropriately introducing internal mismatches. Mismatches in the central region (green) promote RISC loading and mismatches in the seed region (blue) promote unwinding. The functional asymmetry of the duplex is enhanced by 5′ and seed mismatches. Open circles indicate the modified nucleotides on the passenger strand to introduce mismatches.