Abstract: The invention provides a method of suppressing gene expression, comprising providing a mammalian cell with a suppression target RNA molecule comprising a heterologous RNAi target site operatively linked to a RNA sequence from a gene of interest, or with a DNA encoding said suppression target RNA molecule; providing to the cell an inhibitory RNA that has a complementary nucleotide sequence to the heterologous RNAi target site; wherein binding of the inhibitory RNA to the heterologous RNAi target site suppresses gene expression of the operatively linked RNA sequence from the gene of interest; and wherein said heterologous RNAi target site has a size of at least 18 nucleotides in length. The invention further provides nucleic acids and cells suitable for such a method.