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Abstract

The use of electric pulses to transfect all types of cells is well known and regularly used in vitro for bacteria and eukaryotic cells transformation. Electric pulses can also be delivered in vivo either transcutaneously or with electrodes in direct contact with the tissues. After injection of naked DNA in a tissue, appropriate local electric pulses can result in a very high expression of the transferred genes. This manuscript describes the evolution in the concepts and the various optimization steps that have led to the use of combinations of pulses that fit with the known roles of the electric pulses in DNA electrotransfer, namely cell electropermeabilization and DNA electrophoresis. A summary of the main applications published until now is also reported, restricted to the in vivo preclinical trials using therapeutic genes.

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Gene transfer into muscle by electroporation in vivo.

J. Miyazaki, H Aihara (1998)

Among the nonviral techniques for gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple, inexpensive, and safe. Applications of this method have been limited by the relatively low expression levels of the transferred gene. We investigated the applicability of in vivo electroporation for gene transfer into muscle, using plasmid DNA expressing interleukin-5 (IL-5) as the vector. The tibialis anterior muscles of mice were injected with the plasmid DNA, and then a pair of electrode needles were inserted into the DNA injection site to deliver electric pulses. Five days later, the serum IL-5 levels were assayed. Mice that did not receive electroporation had serum levels of 0.2 ng/ml. Electroporation enhanced the levels to over 20 ng/ml. Histochemical analysis of muscles injected with a lacZ expression plasmid showed that in vivo electroporation increased both the number of muscle fibers taking up plasmid DNA and the copy number of plasmids introduced into the cells. These results demonstrate that gene transfer into muscle by electroporation in vivo is more efficient than simple intramuscular DNA injection.

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Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability.

B. Esposito, Y Chvatchko, A Corbaz … (2001)

Interleukin (IL)-18 is the interferon-gamma-inducing factor and has other proinflammatory properties. The precise role of IL-18 in immunoinflammatory diseases remains poorly understood. In this study, we show that in vivo electrotransfer of an expression-plasmid DNA encoding for murine IL-18 binding protein (BP) (the endogenous inhibitor of IL-18) prevents fatty streak development in the thoracic aorta of apoE knockout mice and slows progression of advanced atherosclerotic plaques in the aortic sinus. More importantly, transfection with the IL-18BP plasmid induces profound changes in plaque composition (decrease in macrophage, T cell, cell death, and lipid content and increase in smooth muscle cell and collagen content) leading to a stable plaque phenotype. These results identify for the first time a critical role for IL-18/IL-18BP regulation in atherosclerosis and suggest a potential role for IL-18 inhibitors in reduction of plaque development/progression and promotion of plaque stability. The full text of this article is available at http://www.circresaha.org.

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Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation.

Anita Gothelf, Lluis Mir, Julie Gehl (2003)

Over the last decade a new cancer treatment modality, electrochemotherapy, has emerged. By using short, intense electric pulses that surpass the capacitance of the cell membrane, permeabilization can occur (electroporation). Thus, molecules that are otherwise non-permeant can gain direct access to the cytosol of cells in the treated area.A highly toxic molecule that does not usually pass the membrane barrier is the hydrophilic drug bleomycin. Once inside the cell, bleomycin acts as an enzyme creating single- and double-strand DMA-breaks. The cytotoxicity of bleomycin can be augmented several 100-fold by electroporation. Drug delivery by electroporation has been in experimental use for cancer treatment since 1991. This article reviews 11 studies of electrochemotherapy of malignant cutaneous or subcutaneous lesions, e.g., metastases from melanoma, breast or head- and neck cancer. These studies encompass 96 patients with altogether 411 malignant tumours. Electroporation was performed using plate or needle electrodes under local or general anaesthesia. Bleomycin was administered intratumourally or intravenously prior to delivery of electric pulses. The rates of complete response (CR) after once-only treatments were between 9 and 100% depending on the technique used. The treatment was well tolerated and could be performed on an out-patient basis.

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PubMed ID:: 15454955

DOI:: 10.1038/sj.gt.3302367

ScienceOpen disciplines: Chemistry

Keywords: Animals,DNA,administration & dosage,Electroporation,methods,Gene Expression,Genetic Therapy,Humans,Models, Animal,Muscle, Skeletal,metabolism,Transfection

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ScienceOpen disciplines: Chemistry

Keywords: Animals, DNA, administration & dosage, Electroporation, methods, Gene Expression, Genetic Therapy, Humans, Models, Animal, Muscle, Skeletal, metabolism, Transfection

DNA electrotransfer: its principles and an updated review of its therapeutic applications.

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Most cited references 136

Gene transfer into muscle by electroporation in vivo.

Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability.

Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation.

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