RNA interference (RNAi), a form of post-transcriptional gene silencing induced by introduction of double-stranded RNA (dsRNA), has become a powerful experimental tool for studying gene function. The RNAi phenomenon was first discovered in Caenorhabditis elegans and is characterized by sequence-specific gene silencing elicited by introduction of dsRNA (Fire et al. 1998; Elbashir et al. 2001) complementary to a target mRNA. In the endogenous RNAi pathway, long dsRNA is cleaved by the RNase III type endonuclease, Dicer, to produce 21–23 base pair (bp) short interfering RNAs. The siRNAs are in turn unwound and incorporated into a multiprotein complex known as the RNA-induced silencing complex (RISC), generating a sequence-specific nuclease that guides the cleavage of specific complementary mRNAs. In mammalian cells, direct introduction of siRNAs is used to experimentally initiate RNAi, because introduction of long dsRNA induces a potent antiviral response in addition to RNAi.
MicroRNAs (miRNAs) are small RNA molecules encoded in the genomes of plants and animals. These newly identified molecules are highly conserved RNAs, up to 22 nucleotides in length, that regulate the expression of genes by binding to the 3′-untranslated regions (3′-UTR) of specific mRNAs. Recent studies of miRNA expression implicate miRNAs in brain development, chronic lymphocytic leukemia, colonic adenocarcinoma, Burkitt’s Lymphoma, and viral infection suggesting possible links between miRNAs and viral disease, neurodevelopment, and cancer. Application of microRNAs as therapeutic targets represent a novel molecular based approach for developing new medicines. While siRNA molecules can target only a single gene for disease treatment, microRNA-based therapeutics will have an advantage of a single microRNA targeting a network of genes with minimal off-target side effects, since miRNAs are naturally expressed in human cells.