"The RNAi revolution" provides a concise, readable overview of short RNA-directed silencing processes across multiple organisms. It is an accessible introduction to the history, mechanisms, applications, and current trends in a rapidly advancing field. By one recent estimate, more than 30% of protein coding genes in humans have binding sites for endogenous microRNAs. Thus, an increasing number of scientists are studying processes affected by RNAi. Since RNAi is being widely used as a tool to study biological processes, an increasing number of scientists are interested in recent technological advances in the use of RNAi. The broad scope of "The RNAi revolution" lends itself to citation across the entire RNAi field.

RNAi is a recently reported and very interesting natural pathway to silence gene expression. In addition, RNAi is a very powerful molecular biological tool to discover gene functions. As a tool, RNAi segues with current trends in science toward systematic approaches to discover gene function. It also segues with another current trend in science toward the use of viruses to deliver genes into cells that are difficult to transduce. Thus, RNAi may be used to discover individual gene functions and networks of gene function in primary cells that are physiologically representative of natural conditions. This use of RNAi has moved so rapidly that several genomic collections of viruses expressing short RNAs against every gene in the mouse and human genomes already exist and are commercially available. Furthermore, early indications suggest that short RNAs hold promise for therapeutic applications. That is, clinicians are already inquiring about using RNAi to silence genes that promote disease. In fact, one application of short RNAs in the treatment of macular degeneration is already underway in clinical trials.

"The RNAi revolution" is a short description of the history, mechanisms and applications of an ancient and nearly ubiquitous process. If you imagine that RNAi is like the volume knob on a radio, RNAi turns down the volume of gene expression. In RNAi, the volume knob is short RNAs. Though RNAi is nearly universal, different organisms use several distinct strategies to turn down the volume of gene expression. In some cases short RNAs cut up intermediates in gene expression. In other cases, short RNAs halt the last step of gene expression without cutting up the intermediate. Still, in other cases, short RNAs interact with DNA to either modify the DNA or, in one case, even cut up the DNA. Though short RNAs may use different strategies, the end result is the same: the volume of specific genes is tuned down. These different mechanisms indicate that short RNAs are highly flexible and very potent. For these reasons, and because the RNAi pathways are naturally occurring, short RNAs are being widely used to discover gene expression and also hold the promise for applications in clinical settings.

Dr. Philip Sharp is a 1993 Nobel Prize Laureate in Physiology and Medicine with a long history of investigating the molecular aspects of regulated gene expression. He has always been intrigued by novel biological mechanisms that that are difficult to solve and about which very little is known. Shortly after 1998 when Dr. Andy Fire (Dr. Sharp’s former graduate student) and Dr. Craig Mello first described RNAi in worms, Dr. Sharp and colleagues proceeded to describe the first RNAi reactions in vitro. Shortly thereafter, Dr. Gregory Hannon and colleagues cloned Dicer, the triggering molecule for RNAi. In 2000, when Dr. Carl Novina joined Dr. Sharp’s laboratory, very little was understood about the molecular mechanisms of RNAi. Dr. Novina was intrigued by the phenomenon of gene silencing and the potential power of short RNAs as a molecular biological tool. Dr. Sharp encouraged him to pursue the biological roles, molecular mechanisms, and applications of a natural phenomenon that was almost entirely unknown in mammals.