Targeting tumor gene by shRNA-expressing Salmonella-mediated RNAi
| Autor: | Jie Lin Zhang, Chiang J. Li, Thu Nguyen, Johannes Fruehauf, Andrew C. Keates, Hongnian Guo, C Inal |
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| Rok vydání: | 2010 |
| Předmět: |
Genetic enhancement
Genetic Vectors Biology Small hairpin RNA Mice Salmonella RNA interference Cell Line Tumor Neoplasms Genetics Animals Gene silencing Gene Silencing RNA Small Interfering Molecular Biology beta Catenin Gene knockdown Gene targeting biology.organism_classification Molecular biology RNA Bacterial Salmonella enterica Cell culture Gene Targeting Molecular Medicine RNA Interference Genes Neoplasm |
| Zdroj: | Gene Therapy. 18:95-105 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | 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 APC(Min) 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. |
| Databáze: | OpenAIRE |
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