All eukaryotic organisms share similar mechanisms for information transfer from DNA to RNA to protein. RNA interference represents an efficient mechanism for inactivating this transfer process for a specific targeted gene. Targeting is mediated by the sequence of the RNA molecule introduced to the cell. Double-stranded (ds) RNA can induce sequence-specific inhibition of gene function (genetic interference) in several organisms including the nematode, C. elegans (Fire, et al., 1998, Nature 391:806-811), plants, trypanosomes, Drosophila, and planaria (Waterhouse et al., 1998, Proc. Natl. Acad. Sci. USA 94:13959-13964; Ngo et al., 1998, Proc. Natl. Acad. Sci. USA 95:14687-14692; Kennerdell and Carthew, 1998, Cell 95:1017-1026; Misquitta and Patterson, 1999, Proc. Natl. Acad. Sci. USA 96: 1451-1456; Sanchez-Alvorado and Newmark, 1999, Proc. Natl. Acad. Sci. USA 96:5049-5054). The discovery that dsRNA can induce genetic interference in organisms from several distinct phyla suggests a conserved mechanism and perhaps a conserved physiological role for the interference process. Although several models of RNAi have been proposed (Baulcombe, 1999, Curr. Biol. 9:R599-R601; Sharp, 1999, Genes & Dev. 13:139-141) the mechanisms of action of specific components of the pathway are not known.
Attempts to overexpress a gene (e.g., a transgene) often lead only to transient expression of the gene. Furthermore, the even more undesirable effect of “cosuppression” can occur in which a corresponding endogenous copy of the transgene becomes inactivated. In some cases, transgene silencing leads to problems with the commercial or therapeutic application of transgenic technology to alter the genetic makeup of a cell, organism, or human patient.