A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer
Electrochemotherapy is an efficient method for the local treatment of cutaneous and subcutaneous metastases, but its efficacy as a systemic treatment remains low. The application of gene electrotransfer (GET) to transfer DNA coding for immune system modulating molecules could allow for a systemic ef...
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doaj-94c412fb34684b44b73ca9ca8f5bf7962020-11-25T01:54:18ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-08-012016404710.3390/ijms20164047ijms20164047A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA ElectrotransferSonam Chopra0Paulius Ruzgys1Milda Jakutaviciute2Aiste Rimgailaite3Diana Navickaitė4Saulius Satkauskas5Biophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos st. 8, LT-44404 Kaunas, LithuaniaBiophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos st. 8, LT-44404 Kaunas, LithuaniaBiophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos st. 8, LT-44404 Kaunas, LithuaniaBiophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos st. 8, LT-44404 Kaunas, LithuaniaBiophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos st. 8, LT-44404 Kaunas, LithuaniaBiophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos st. 8, LT-44404 Kaunas, LithuaniaElectrochemotherapy is an efficient method for the local treatment of cutaneous and subcutaneous metastases, but its efficacy as a systemic treatment remains low. The application of gene electrotransfer (GET) to transfer DNA coding for immune system modulating molecules could allow for a systemic effect, but its applications are limited because of possible side effects, e.g., immune system overactivation and autoimmune response. In this paper, we present the simultaneous electrotransfer of bleomycin and plasmid DNA as a method to increase the systemic effect of bleomycin-based electrochemotherapy. With appropriately selected concentrations of bleomycin and plasmid DNA, it is possible to achieve efficient cell transfection while killing cells via the cytotoxic effect of bleomycin at later time points. We also show the dynamics of both cell electrotransfection and cell death after the simultaneous electrotransfer of bleomycin and plasmid DNA. Therefore, this method could have applications in achieving the transient, cell death-controlled expression of immune system activating genes while retaining efficient bleomycin mediated cell killing.https://www.mdpi.com/1422-0067/20/16/4047gene electrotransfercell deathbleomycinplasmid DNAtransfectioncytotoxic effect |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sonam Chopra Paulius Ruzgys Milda Jakutaviciute Aiste Rimgailaite Diana Navickaitė Saulius Satkauskas |
spellingShingle |
Sonam Chopra Paulius Ruzgys Milda Jakutaviciute Aiste Rimgailaite Diana Navickaitė Saulius Satkauskas A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer International Journal of Molecular Sciences gene electrotransfer cell death bleomycin plasmid DNA transfection cytotoxic effect |
author_facet |
Sonam Chopra Paulius Ruzgys Milda Jakutaviciute Aiste Rimgailaite Diana Navickaitė Saulius Satkauskas |
author_sort |
Sonam Chopra |
title |
A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer |
title_short |
A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer |
title_full |
A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer |
title_fullStr |
A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer |
title_full_unstemmed |
A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer |
title_sort |
novel method for controlled gene expression via combined bleomycin and plasmid dna electrotransfer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-08-01 |
description |
Electrochemotherapy is an efficient method for the local treatment of cutaneous and subcutaneous metastases, but its efficacy as a systemic treatment remains low. The application of gene electrotransfer (GET) to transfer DNA coding for immune system modulating molecules could allow for a systemic effect, but its applications are limited because of possible side effects, e.g., immune system overactivation and autoimmune response. In this paper, we present the simultaneous electrotransfer of bleomycin and plasmid DNA as a method to increase the systemic effect of bleomycin-based electrochemotherapy. With appropriately selected concentrations of bleomycin and plasmid DNA, it is possible to achieve efficient cell transfection while killing cells via the cytotoxic effect of bleomycin at later time points. We also show the dynamics of both cell electrotransfection and cell death after the simultaneous electrotransfer of bleomycin and plasmid DNA. Therefore, this method could have applications in achieving the transient, cell death-controlled expression of immune system activating genes while retaining efficient bleomycin mediated cell killing. |
topic |
gene electrotransfer cell death bleomycin plasmid DNA transfection cytotoxic effect |
url |
https://www.mdpi.com/1422-0067/20/16/4047 |
work_keys_str_mv |
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