Approaches to endogenous expression of siRNAs in mammalian cells. (a) Sense and antisense strand of the siRNA duplex are expressed from separate promoters. (b) siRNA duplex is expressed as a stem-loop structure (small hairpin RNA [shRNA]) from a single promotor. Sense and antisense strands are separated by a loop-forming spacer. The construct is further processed by Dicer within the cell to form a functional siRNA. In both cases transcription is terminated by six consecutive thymidine residues.