Letter abstract

Nature Biotechnology 24, 697 - 702 (2006)
Published online: 14 May 2006 | doi:10.1038/nbt1211

Short hairpin RNA–expressing bacteria elicit RNA interference in mammals

Shuanglin Xiang1,2, Johannes Fruehauf1,2 & Chiang J Li1


RNA-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 β-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.

  1. 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 to: Chiang J Li1 e-mail: cli@BIDMC.harvard.edu


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