Nature Biotechnology 24, 697 - 702 (2006)
Published online: 14 May 2006; | doi:10.1038/nbt1211
Short hairpin RNA–expressing bacteria elicit RNA interference in mammalsShuanglin Xiang1, 2, Johannes Fruehauf1, 2
& Chiang J Li11
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, Massachusetts 02215, USA. 2
These authors contributed equally to this work.
Correspondence should be addressed to Chiang J Li cli@BIDMC.harvard.edu InvHlyACTNNB1RNA-interference (RNAi) is a potent mechanism, conserved from plants to humans for specific silencing of genes, which holds promise for functional genomics and gene-targeted therapies. Here we show that bacteria engineered to produce a short hairpin RNA (shRNA) targeting a mammalian gene induce trans-kingdom RNAi in vitro and in vivo. Nonpathogenic Escherichia coli were engineered to transcribe shRNAs from a plasmid containing the invasin gene Inv and the listeriolysin O gene HlyA, which encode two bacterial factors needed for successful transfer of the shRNAs into mammalian cells. Upon oral or intravenous administration, E. coli encoding shRNA against CTNNB1 (catenin  -1) induce significant gene silencing in the intestinal epithelium and in human colon cancer xenografts in mice. These results provide an example of trans-kingdom RNAi in higher organisms and suggest the potential of bacteria-mediated RNAi for functional genomics, therapeutic target validation and development of clinically compatible RNAi-based therapies.
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