Electric Pulse‐Mediated Gene Delivery to Various Animal Tissues

Mir, Lluis M.; Møller, Pia Krause; André, Franck; Gehl, Julie

doi:10.1016/s0065-2660(05)54005-7

Cited by 129 publications

(81 citation statements)

References 169 publications

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“…[36][37][38] The most successful cases occur after intranasal or intratracheal administration, when targeting airway epithelial cells. 3,5,9,39 Tissues containing nondividing cells (as in muscle) or slow mitotic cells (as in the liver) are very attractive targets because pDNA can remain for a long time inside the cells. 40 In relation to the relatively fast kinetics seen here, we do not exclude the possibility that the decrease in expression after 5-7 days may be indicative of toxicity.…”

Section: Discussionmentioning

confidence: 99%

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Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

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The lack of efficient in vivo gene delivery is a well-known shortcoming of nonviral delivery vectors, in particular of chemical vectors. We developed a series of novel nonviral carriers for plasmid-based in vivo gene delivery. This new transport device is based on the assembly of DNA plasmids with synthetic derivatives of naturally occurring moleculesfatty acid-spermine conjugates (or lipospermines). We tested the ability of these fatty acid conjugates to interact with plasmid DNA (pDNA) and found that they formed DNA nanocomplexes, which are protected from DNase I degradation. This protection was shown to directly correlate with the length of the aliphatic component. However, this increase in the length of the hydrocarbon chain resulted in increased toxicity. The cationic lipids used for transfection typically have a C 16 and C 18 hydrocarbon chain. Interestingly, toxicity studies, together with further characterization studies, suggested that the two most suitable candidates for in vivo delivery are those with the shortest hydrocarbon chain, butanoyl-and decanoylspermine. Morphological characterization of DNA nanocomplexes resulting from these lipospermines showed the formation of a homogenous population, with the diameter ranging approximately from 40 to 200 nm. Butanoylspermine was found to be the most promising carrier from this series, resulting in a significantly increased gene expression, in relation to naked plasmid, in both tissues herein targeted (dermis and M. tibialis anterior). Thus, we established a correlation between the in vitro properties of the ensuing DNA nanocarriers and their efficient in vivo gene expression.

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Section: Discussionmentioning

confidence: 99%

“…Physical methods have been shown to be highly efficient in targeting several tissues, especially skeletal muscle or cancer tissues. [1][2][3][4] Yet, all the electrical equipments used in this method present some inconveniences. Chemical vectors are, therefore, an alternative and are the focus of this work.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

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“…Electroporation-permeabilization of membranes by electrical pulses-has become an expanding research field, both within nonthermal irreversible electroporation from which cell membranes do not recover and cell death ensues (3,4,(7)(8)(9), and within reversible electroporation where cell membranes do reseal and only transiently allow drugs (10,11) or genes (12)(13)(14)(15)(16)(17)(18)(19)(20) to enter the otherwise intact cell.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Validation of Electrochemotherapy as an Effective Treatment for Brain Tumors

et al. 2011

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Electrochemotherapy represents a strategy to enhance chemotherapeutic drug uptake by delivering electrical pulses which exceed the dielectric strength of the cell membrane, causing transient formation of structures that enhance permeabilization. Here we show that brain tumors in a rat model can be eliminated by electrochemotherapy with a novel electrode device developed for use in the brain. By using this method, the cytotoxicity of bleomycin can be augmented more than 300-fold because of increased permeabilization and more direct passage of drug to the cytosol, enabling highly efficient local tumor treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment, we found that 9 of 13 rats (69%) receiving electrochemotherapy displayed a complete elimination of tumor, in contrast to control rats treated with bleomycin only, pulses only, or untreated where tumor progression occurred in each case. Necrosis induced by electrochemotherapy was restricted to the treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool to treat primary brain tumors and brain metastases. Cancer Res; 71(11); 3753-62. Ó2011 AACR.

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“…[14][15][16] Electrically assisted gene delivery, called electrotransfection, increased transfection efficiency of either reporter genes or therapeutic genes compared with injection of gene alone. 17,18 To date several preclinical and clinical studies using electroporation (EP) and therapeutic genes for cancer treatment led to encouraging results demonstrating antitumor effectiveness. [19][20][21][22] Owing to high mutation rate of K-ras also in colorectal cancer, silencing of K-ras in colorectal cancer is an attractive therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

et al. 2010

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Mutations of K-ras have been found in 30-60% of colorectal carcinomas and are believed to be associated with tumor initiation, tumor progression and metastasis formation. Therefore, silencing of mutant K-ras expression has become an attractive therapeutic strategy for colorectal cancer treatment. The aim of our study was to investigate the effect of microRNA (miRNA) molecules directed against K-ras (miRNA-K-ras) on K-ras expression level and the growth of colorectal carcinoma cell line LoVo in vitro and in vivo. In addition, we evaluated electroporation as a gene delivery method for transfection of LoVo cells and tumors with plasmid DNA encoding miRNA-K-ras (pmiRNA-K-ras). Results of our study indicated that miRNAs targeting K-ras efficiently reduced K-ras expression and cell survival after in vitro electrotransfection of LoVo cells with pmiRNA-K-ras. In vivo, electroporation has proven to be a simple and efficient delivery method for local administration of pmiRNA-K-ras molecules into LoVo tumors. This therapy shows pronounced antitumor effectiveness and has no side effects. The obtained results demonstrate that electrogene therapy with miRNA-K-ras molecules can be potential therapeutic strategy for treatment of colorectal cancers harboring K-ras mutations.

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Electric Pulse‐Mediated Gene Delivery to Various Animal Tissues

Cited by 129 publications

References 169 publications

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Preclinical Validation of Electrochemotherapy as an Effective Treatment for Brain Tumors

MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

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