Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Andrew Fire (), SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver and Craig C. Mello
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Andrew Fire: Carnegie Institution of Washington
SiQun Xu: Carnegie Institution of Washington
Mary K. Montgomery: Carnegie Institution of Washington
Steven A. Kostas: Carnegie Institution of Washington
Samuel E. Driver: Program in Molecular Medicine, University of Massachusetts Cancer Center
Craig C. Mello: Program in Molecular Medicine, University of Massachusetts Cancer Center

Nature, 1998, vol. 391, issue 6669, 806-811

Abstract: Abstract Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene1,2. Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts. RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression3,4. Here we investigate the requirements for structure and delivery of the interfering RNA. To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference. The effects of this interference were evident in both the injected animals and their progeny. Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.

Date: 1998
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DOI: 10.1038/35888

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