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JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 753-756
© 2003 The British Society for Antimicrobial Chemotherapy


Leading Article

siRNAs: a new wave of RNA-based therapeutics

Glen A. Coburn and Bryan R. Cullen*

Howard Hughes Medical Institute, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27701, USA

Keywords: antiviral, RNA, interference

The first 150 words of the full text of this article appear below.


    Introducing silence
 
In 1998, Fire et al.1 made the startling discovery that double-stranded RNA (dsRNA) could induce a potent silencing effect on homologous genes in the nematode Caenorhabditis elegans. This technique, termed RNA interference (RNAi), has proved to be a powerful tool with which to dissect gene function in plants, C. elegans and Drosophila. Although RNAi is evolutionarily conserved among plants and animals, silencing of specific genes in mammalian cells has been difficult because of the induction of the interferon response by dsRNAs of >=30 nt.2,3 This non-specific response to dsRNA leads to global changes in cellular gene expression and apoptosis, masking any specific silencing effect by RNAi in mammalian cells. Recently, however, it was shown that potent and specific gene silencing could be achieved in human cells transfected with small interfering RNAs (siRNA) of 21–23 nt, a key intermediate in the RNAi pathway.4 This landmark discovery by Tuschl . . . [Full Text of this Article]


    RNAi-mediated inhibition of viral replication
 

    Conclusions and future challenges
 

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