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Targeting tumor gene by shRNA-expressing Salmonella-mediated RNAi

Gene Therapy volume 18, pages 95–105 (2011)Cite this article

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An Erratum to this article was published on 10 March 2011

A Corrigendum to this article was published on 11 November 2010

Abstract

RNA interference (RNAi) has been established as an important research tool that carries great potential for gene therapy. However, targeted induction of RNAi in vivo has met with significant challenges. In this study, a novel pSLS plasmid capable of expressing short hairpin RNAs (shRNAs) was transformed into attenuated Salmonella enterica serovar typhimurium strain 7207 (SL). In vitro infection studies with the transformed S. enterica containing pSLS (SL-pSLS-CAT) demonstrated that expression of shRNA targeting the CTNNB1 gene induced potent and specific silencing of CTNNB1 expression in cultured SW480 cells. CTNNB1 knockdown in SW480 cells was associated with markedly reduced proliferation and cell death compared with that of control infected cells. In addition, SL-pSLS-CAT-mediated CTNNB1 knockdown markedly reduced tumor growth in SW480 xenograft mice. These tumors exhibited reduced levels of CTNNB1, as well as c-Myc and cyclin D1. Finally, SL-pSLS-CAT treatment also resulted in reduced expression levels of these genes in polyps, mucosal tissues and in small intestines of APCMin mice. Taken together, these data suggest that attenuated shRNA-expressing Salmonella may be a powerful new tool for in vitro gene silencing, functional genomics, and the development of RNAi-based anticancer or human immunodeficiency virus therapeutics.

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Acknowledgements

We thank Thu Nguyen for her instruction of in vivo experiment; Dr Johannes Fruehauf, Dr Andrew Keates and Dr John R Nambu for their help in English language; Natalya Bodyak for animal feeding and genotyping work; and Dr Cengz for reformating the figures.

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Author notes

  1. H Guo and J Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Gastroenterology, Skip Ackerman Center for Molecular Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    H Guo, J Zhang & C Inal

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  1. H Guo
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Correspondence to H Guo.

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Guo, H., Zhang, J. & Inal, C. Targeting tumor gene by shRNA-expressing Salmonella-mediated RNAi. Gene Ther 18, 95–105 (2011). https://doi.org/10.1038/gt.2010.112

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