Long interfering nucleic acid (iNA) duplexes, which are at least 30 nucleotides in length, which have at least one nick or nucleotide gap in the antisense or the sense strands or in both the sense and antisense strands. These long iNA duplexes do not induce an interferon response when transfected into mammalian cells. The antisense strands can target two separate mRNAs or two segments of one mRNA.