Short hairpin RNA-expressing bacteria elicit RNA interference in mammals.

Abstract:

: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 beta-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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Xiang S,Fruehauf J,Li CJ

doi

10.1038/nbt1211

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

697-702

issue

6

eissn

1087-0156

issn

1546-1696

pii

nbt1211

journal_volume

24

pub_type

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