POTENT AND SPECIFIC GENETIC INTERFERENCE BY DOUBLE-STRANDED-RNA IN CAENORHABDITIS-ELEGANS

Experimental introduction of RNA into cells can be used in certain bio logical systems to interfere with function of an endogenous gene(1,2). Such effects have been proposed io result from a simple antisense mec hanism that depends on hybridization between the injected RNA and endo genous messenger RNA transcripts, RNA interference has been used in th e nematode Caenorhabditis elegans to manipulate gene expression(3,4). Here we investigate the requirements for structure and delivery of the interfering RNA. To our surprise, we found that double-stranded RNA w as substantially more effective at producing interference than was eit her strand individually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mi xtures caused potent and specific interference. The effects of this in terference were evident in bath the injected animals and their progeny . Only a few molecules of injected double-stranded RNA were required p er affected cell, arguing against stochiometric interference with endo genous mRNA and suggesting that there could be a catalytic or amplific ation component in the interference process.