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Oneof the best ways to find out what a gene does is to shut it off and see whatgoes wrong--often an arduous task. Now researchers have developed a new methodfor silencing specific genes in mammalian cells. Although still in its infancy,the approach, known as RNA interference (RNAi), could speed up geneticresearch.

Like much ofmolecular biology, the technique was inspired by nature. A variety oforganisms, including plants, fruit flies, the roundworm Caenorhabditiselegans, and likely mammals, seem to enlist RNAi naturally to fight offviruses and restrain the movement of pieces of DNA that can hop around anddisrupt a genome (Science, 26 May 2000, p. 1370).In RNAi, double-stranded RNA molecules target a messenger RNA with acorresponding sequence and cause it to be chewed up, thus preventing themessenger RNA from making its protein.

Recentlyscientists have harnessed this process as a research tool, injectingdouble-stranded RNA into worm and fly cells to turn off specific genes. But sofar, silencing genes using RNAi has not worked well in mammalian cells;although the approach has been successful in mouse embryos, double-stranded RNAshuts down synthesis of all proteins, not just the target gene, in other typesof mammalian cells.

Now scientistsat the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany,report in the 24 May issue of Nature that they have finally overcomethis barrier. They use specially constructed double-stranded RNA moleculescalled siRNAs that are much shorter than those used previously. In four celllines derived from human and monkey, siRNAs substantially lowered theexpression of three of four test genes--by as much as 90%. Though the techniquewon¡®t replace gene knockout strategies, in which an animal is engineered tolack a certain gene entirely, RNAi is faster and easier. Furthermore, genes thatare lethal when knocked out in embryos can be analyzed with RNAi in cellculture.

"It¡¯sgoing to totally revolutionize somatic cell genetics in mammals," predictsPhillip Zamore of the University of Massachusetts Medical Center in Worcester."Instead of devoting 6 months to a year figuring out how to turn offexpression [of a mammalian gene], people will be able to go in and in a weekturn off the expression of 10 genes."

--R. JOHN DAVENPORT

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