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Updated: Jun 24, 2026
Bacterial Delivery of RNAi Effectors: Transkingdom RNAi
Published on: August 18, 2010
Bacterial delivery of siRNAs: a new approach to solid tumor therapy
De-Qi Xu1, Ling Zhang, Dennis J Kopecko
1Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
Abstract:
RNAi is a powerful research tool for specific gene silencing and may also lead to promising novel therapeutic strategies. However, the development of RNAi-based therapies has been slow due to the lack of targeted delivery methods. The biggest challenge in the use of siRNA-based therapies is the delivery to target cells. There are many additional obstacles to in vivo delivery of siRNAs, such as degradation by endogenous enzymes and interaction with blood components leading to nonspecific uptake into cells, which govern biodistribution and availability of siRNA in the body. Naked unmodified synthetic siRNA including plasmid-carried-shRNA-expression constructs cannot penetrate cellular membranes, and therefore, systemic application is unlikely to be successful. The success of gene therapy by siRNAs relies on the development of safe, economical, and efficacious in vivo delivery systems into the target cells. Attenuated Salmonella have been employed recently as vectors to deliver silencing hairpin RNA (shRNA) expression plasmids into mammalian cells. This approach has achieved gene silencing in vitro and in vivo. The facultative anaerobic, invasive Salmonella have a natural tropism for solid tumors including metastatic tumors. Genetically modified, attenuated Salmonella have been used recently both as potential antitumor agents by themselves, and to deliver specific tumoricidal therapies. This chapter describes the use of attenuated bacteria as tumor-targeting delivery systems for cancer therapy.
Insights
Attenuated Salmonella bacteria show promise for delivering gene-silencing RNA into cancer cells. This novel approach overcomes challenges in targeted delivery for RNA interference (RNAi) cancer therapies.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Therapy
Background:
- RNA interference (RNAi) is a key tool for gene silencing, with therapeutic potential.
- Developing effective RNAi therapies is hindered by challenges in targeted delivery and in vivo stability of small interfering RNA (siRNA).
- Current methods like naked siRNA and plasmid constructs struggle with cellular membrane penetration and systemic delivery.
Purpose of the Study:
- To explore the use of attenuated Salmonella as a delivery system for RNAi-based cancer therapy.
- To overcome the limitations of current siRNA delivery methods for in vivo applications.
- To investigate the potential of Salmonella's natural tumor tropism for targeted cancer treatment.
Main Methods:
- Utilizing genetically modified, attenuated Salmonella bacteria as vectors.
- Administering silencing hairpin RNA (shRNA) expression plasmids via Salmonella.
- Evaluating gene silencing efficacy in vitro and in vivo.
Main Results:
- Successful gene silencing was achieved in both in vitro and in vivo models.
- Attenuated Salmonella demonstrated effective delivery of shRNA expression plasmids into mammalian cells.
- Salmonella's natural tropism for solid and metastatic tumors was leveraged for targeted delivery.
Conclusions:
- Attenuated Salmonella serve as a viable and effective delivery system for RNAi therapeutics.
- This bacterial vector approach offers a promising strategy to overcome in vivo delivery challenges for cancer gene therapy.
- The combination of Salmonella's tumor-targeting ability and RNAi technology presents a novel platform for cancer treatment.
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