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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Replicase-based plasmid DNA shows anti-tumor activity

Authors: B Leticia Rodriguez, Zhen Yu, Woon-Gye Chung, Richard Weiss, Zhengrong Cui

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Double stranded RNA (dsRNA) has multiple anti-tumor mechanisms. Over the past several decades, there have been numerous attempts to utilize synthetic dsRNA to control tumor growth in animal models and clinical trials. Recently, it became clear that intracellular dsRNA is more effective than extracellular dsRNA on promoting apoptosis and orchestrating adaptive immune responses. To overcome the difficulty in delivering a large dose of synthetic dsRNA into tumors, we propose to deliver a RNA replicase-based plasmid DNA, hypothesizing that the dsRNA generated by the replicase-based plasmid in tumor cells will inhibit tumor growth.

Methods

The anti-tumor activity of a plasmid (pSIN-β) that encodes the sindbis RNA replicase genes (nsp1-4) was evaluated in mice with model tumors (TC-1 lung cancer cells or B16 melanoma cells) and compared to a traditional pCMV-β plasmid.

Results

In cell culture, transfection of tumor cells with pSIN-β generated dsRNA. In mice with model tumors, pSIN-β more effectively delayed tumor growth than pCMV-β, and in some cases, eradicated the tumors.

Conclusion

RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth.
Appendix
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Metadata
Title
Replicase-based plasmid DNA shows anti-tumor activity
Authors
B Leticia Rodriguez
Zhen Yu
Woon-Gye Chung
Richard Weiss
Zhengrong Cui
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-110

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