A method of regulating expression, the method comprising: providing to a cell a nucleotide construct, wherein said nucleotide construct comprises: a first and a second nucleotide sequence that hybridize to form the stem of a stem-loop structure, and a third nucleotide sequence disposed between the first and second nucleotide sequences, and splice sites operationally placed and oriented so as to allow the cleavage of the loop portion of the stem-loop structure from the stem portion of the stem-loop structure, wherein the first and second nucleotide sequences, when paired, generate a small interfering nucleic acid that modulates expression of a target, wherein the third nucleotide sequence is of sufficient length to allow the first and second nucleotide sequences to stably pair with each other, and wherein the third nucleotide sequence comprises an antisense nucleotide sequence capable of modulating the expression of a target through antisense suppression, and wherein the target modulated by the antisense nucleotide sequence and the target modulated by the small interfering nucleic acid may be the same or different; and culturing said cell. providing to a cell a nucleotide construct, wherein said nucleotide construct comprises: a first and a second nucleotide sequence that hybridize to form the stem of a stem-loop structure, and a third nucleotide sequence disposed between the first and second nucleotide sequences, and splice sites operationally placed and oriented so as to allow the cleavage of the loop portion of the stem-loop structure from the stem portion of the stem-loop structure, wherein the first and second nucleotide sequences, when paired, generate a small interfering nucleic acid that modulates expression of a target, wherein the third nucleotide sequence is of sufficient length to allow the first and second nucleotide sequences to stably pair with each other, and wherein the third nucleotide sequence comprises an antisense nucleotide sequence capable of modulating the expression of a target through antisense suppression, and wherein the target modulated by the antisense nucleotide sequence and the target modulated by the small interfering nucleic acid may be the same or different; and culturing said cell. a first and a second nucleotide sequence that hybridize to form the stem of a stem-loop structure, and a third nucleotide sequence disposed between the first and second nucleotide sequences, and splice sites operationally placed and oriented so as to allow the cleavage of the loop portion of the stem-loop structure from the stem portion of the stem-loop structure, wherein the first and second nucleotide sequences, when paired, generate a small interfering nucleic acid that modulates expression of a target, wherein the third nucleotide sequence is of sufficient length to allow the first and second nucleotide sequences to stably pair with each other, and wherein the third nucleotide sequence comprises an antisense nucleotide sequence capable of modulating the expression of a target through antisense suppression, and wherein the target modulated by the antisense nucleotide sequence and the target modulated by the small interfering nucleic acid may be the same or different; and wherein the first and second nucleotide sequences, when paired, generate a small interfering nucleic acid that modulates expression of a target, wherein the third nucleotide sequence is of sufficient length to allow the first and second nucleotide sequences to stably pair with each other, and wherein the third nucleotide sequence comprises an antisense nucleotide sequence capable of modulating the expression of a target through antisense suppression, and wherein the target modulated by the antisense nucleotide sequence and the target modulated by the small interfering nucleic acid may be the same or different; and culturing said cell.