What is RNAi?
Discovered only a few years ago, RNA interference ("RNAi") is a natural mechanism for selectively silencing genes, and it is rapidly advancing as both a target validation tool in drug discovery and as a potential therapeutic. Genes provide cells with instructions for making specific proteins that are "encoded" by that gene. "Silencing" a gene refers to stopping or reducing significantly the production of the specified protein encoded by the target gene that is believed to cause, or contribute to the advance of, a particular disease.

To initiate the process of protein production the cell makes a copy of the gene that encodes for the particular protein. This copy is not made of DNA, but rather ribonucleic acid, or RNA, and is referred to as "messenger" RNA, or mRNA. This mRNA, manufactured in the cell nucleus, travels into the cytoplasm of a cell to organelles responsible for protein synthesis, where it directs the production of a protein based on the DNA sequence carried by the mRNA. When this process works uninterrupted and the protein produced, the gene is said to be "expressed".

drawing by Daniel Kim

RNA interference (RNAi) is a process by which double stranded RNA (dsRNA) directs
sequence-specific degradation of mRNA. Naturally occurring RNAi is initiated by a process in which the dsRNA is cut into smaller pieces between 21 and 25 nucleotides (nt) in length. These small interfering (siRNA) associate with RNAs with several proteins to form what is known as a RNA-induced silencing complex ("RISC"). RISC recognizes and cleaves target mRNAs, destroying their ability to direct the production of the specified protein. Introduction of synthetic 21-nt siRNA duplexes into cells can also trigger RNAi, resulting in transient interference of gene expression in a sequence specific manner. Synthetic siRNA represents a new class of molecules with potentially significant medical applications.