Compositions and methods for down modulating target gene expression which RNA interference, as well as methods for administering said compositions are disclosed. The method comprises administering a first oligonucleotide strand to a cell, incubating the cells for a time period suitable for uptake of the first oligo nucleotide strand prior to administration of a second oligonucleotide strand, wherein the first strand and the second strand form an intracellular duplex which is effective to catalyze degradation of gene target mRNA or inhibit translation of said mRNA.