Schematic representation of the strategies used for combinatorial RNAi. Each method of co-RNAi results in the transcription of dsRNA precursor molecules that encode the siRNA stem (red or blue), a loop sequence and a passenger strand, that are processed into active siRNAs. The top panel shows a multiple promoter/shRNA construct that encodes dual U6 promoters to express two separate shRNAs simultaneously. The middle panel shows a long hairpin RNA (lhRNA) construct that uses a single U6 promoter to express an extended shRNA that encodes two separate siRNA stems. The bottom panel shows a miRNA-embedded construct that uses a single U6 promoter to express a miRNA cluster that features two introduced shRNAs that mimic naturally expressed miRNAs.