Researchers have known for some time that one way to determine what any given gene does is to turn it off and see what happens. Silencing the gene by blocking its so-called messenger RNA¿a technique dubbed RNA interference (RNAi)¿has proved particularly effective in such creatures as nematode worms and fruit flies. In mammalian cells, though, this method seemed to elicit a nonspecific, and therefore uninformative, response¿until now. Findings published today in the journal Nature reveal that RNAi can, in fact, work in mammalian cells. The new results should help scientists study many genes of unknown function that human genome research continues to bring to light.
Researchers induce RNAi in nonmammalian cells by first synthesizing a double-stranded RNA (dsRNA) matching a particular gene sequence and introducing it into a cell, which results in the dsRNA breaking into short pieces. These short interfering RNAs (siRNAs) then trigger the degradation of the matching messenger RNA sequence, thus silencing the gene it belongs to. The new research, conducted by Thomas Tuschl of the University of Gottingen in Germany and his colleagues, reveals that although introducing dsRNA into mammalian cells leads to a nonspecific response, introducing the siRNAs themselves into the cells can initiate RNAi.
RNAi appears to work more effectively than the popular "antisense" techniques for preventing gene expression, although various technical issues must be resolved before it is widely applied to mammalian cells. For one thing, whereas dsRNA can be fed to nematodes for the desired result, delivering siRNAs to mammalian cells is not so simple. All in all, however, the results mark a big step forward. The use of these siRNAs, the researchers write, "holds great promise for analysis of gene function in human cell culture and the development of gene-specific therapeutics."