A Novel Method for Controlled Gene Expression via Combined Bleomycin and Plasmid DNA Electrotransfer

被引：8

作者：

Chopra, Sonam ^{[1
]}

Ruzgys, Paulius ^{[1
]}

Jakutaviciute, Milda ^{[1
]}

Rimgailaite, Aiste ^{[1
]}

Navickaite, Diana ^{[1
]}

Satkauskas, Saulius ^{[1
]}

机构：

[1] Vytautas Magnus Univ, Fac Nat Sci, Biophys Res Grp, Vileikos St 8, LT-44404 Kaunas, Lithuania

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 16期

关键词：

gene electrotransfer; cell death; bleomycin; plasmid DNA; transfection; cytotoxic effect; CANCER-IMMUNOTHERAPY; ELECTROCHEMOTHERAPY; INTERLEUKIN-12; ELECTROPORATION; DELIVERY; THERAPY; COMBINATION; CELLS; CHALLENGES; MOLECULES;

D O I：

10.3390/ijms20164047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：12

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