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.


RNAi has been rapidly adopted for functional genomics, pathway analysis, and drug target validation experiments, and is now being used in high-throughput experiments with large numbers of siRNAs, or siRNA libraries. A key to all successful siRNA experiments is efficient delivery of the siRNA into cells and subsequent uptake of the siRNA by the RISC. RNAi can be successfully elicited in mammalian cells using exogenously derived siRNA only when the correct method and matrix of delivery conditions are employed for the cell type being used. 2006 Nobel Prize in Medicine was awarded for the discovery of RNAi to Andrew Fire and Craig Mello and their original discovery work published in Nature journal: “Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans” – link


There are several hundreds of known microRNAs, some of which are known to play important regulatory roles in animals by targeting the messages of protein-coding genes for translational repression. Misregulation of miRNA expression has an important role in development of many diseases. Although the first work on miRNA appeared in 1993, only recently the diversity of this class of small, regulatory RNAs been appreciated. One miRNA can regulate from a few to hundreds of genes, and since over 1,000 miRNA genes are present in higher eukaryotes, the regulatory gene network is important in various cellular functions. Several research groups have provided evidence that miRNAs regulate many cellular processes, including cell proliferation, apoptosis, differentiation, disease and fat metabolism.

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.