Replicase-based plasmid DNA shows anti-tumor activity

<p>Abstract</p> <p>Background</p> <p>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 be...

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Main Authors: Weiss Richard, Chung Woon-Gye, Yu Zhen, Rodriguez B Leticia, Cui Zhengrong
Format: Article
Language:English
Published: BMC 2011-03-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/11/110
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author Weiss Richard
Chung Woon-Gye
Yu Zhen
Rodriguez B Leticia
Cui Zhengrong
author_facet Weiss Richard
Chung Woon-Gye
Yu Zhen
Rodriguez B Leticia
Cui Zhengrong
author_sort Weiss Richard
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth.</p>
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spelling doaj.art-9b65a55c822f4d0f941562d8c7c685cb2022-12-22T01:37:35ZengBMCBMC Cancer1471-24072011-03-0111111010.1186/1471-2407-11-110Replicase-based plasmid DNA shows anti-tumor activityWeiss RichardChung Woon-GyeYu ZhenRodriguez B LeticiaCui Zhengrong<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth.</p>http://www.biomedcentral.com/1471-2407/11/110
spellingShingle Weiss Richard
Chung Woon-Gye
Yu Zhen
Rodriguez B Leticia
Cui Zhengrong
Replicase-based plasmid DNA shows anti-tumor activity
BMC Cancer
title Replicase-based plasmid DNA shows anti-tumor activity
title_full Replicase-based plasmid DNA shows anti-tumor activity
title_fullStr Replicase-based plasmid DNA shows anti-tumor activity
title_full_unstemmed Replicase-based plasmid DNA shows anti-tumor activity
title_short Replicase-based plasmid DNA shows anti-tumor activity
title_sort replicase based plasmid dna shows anti tumor activity
url http://www.biomedcentral.com/1471-2407/11/110
work_keys_str_mv AT weissrichard replicasebasedplasmiddnashowsantitumoractivity
AT chungwoongye replicasebasedplasmiddnashowsantitumoractivity
AT yuzhen replicasebasedplasmiddnashowsantitumoractivity
AT rodriguezbleticia replicasebasedplasmiddnashowsantitumoractivity
AT cuizhengrong replicasebasedplasmiddnashowsantitumoractivity