<i>In Vivo</i>Electroporation for Gene Therapy

Heller, Loree C.; Heller, Richard

doi:10.1089/hum.2006.17.890

Cited by 211 publications

(139 citation statements)

References 88 publications

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“…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. Therefore, the aim of our study was to identify the effective siRNA molecule against K-ras in human adenocarcinoma cell line LoVo by testing different siRNA sequences.…”

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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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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“…[3][4][5] Gene therapy using electropulsation as a gene delivery method has already entered clinical trials for the treatment of different tumor types in cancer patients and for vaccination. [6][7][8][9] Electrotransfer of plasmid DNA has been assayed and used in many different tissues, such as skin, muscle, liver, tumors, lung, cornea, kidney, brain, cartilage, bladder, carotid artery and tendon. [6][7][8] However, most studies were carried out in muscle, where high transfection efficiencies can be obtained.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] Electrotransfer of plasmid DNA has been assayed and used in many different tissues, such as skin, muscle, liver, tumors, lung, cornea, kidney, brain, cartilage, bladder, carotid artery and tendon. [6][7][8] However, most studies were carried out in muscle, where high transfection efficiencies can be obtained. So far, the transfection efficiencies obtained in tumors following electropulsation have been smaller compared to other tissues, [10][11][12] but a significant therapeutic effect can nevertheless be obtained by electrotransfer of therapeutic genes into tumors.…”

Section: Introductionmentioning

confidence: 99%

Control by pulse parameters of DNA electrotransfer into solid tumors in mice

et al. 2009

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Electrotransfer (electroporation) is recognized as one of the most promising alternatives to viral vectors for transfection of different tissues in vivo for therapeutic purposes. We evaluated the transfection efficiency of reporter genes (green fluorescent protein and luciferase) in murine subcutaneous tumors using different combinations of high-field (HV) (600-1400 V cm À1 , 100 ms, 8 pulses) and low-field (LV) (80-160 V cm À1 , 50-400 ms, 1-8 pulses) pulses and compared it to protocol using eight identical pulses of 600 V cm À1 and 5 ms duration (electro-gene therapy, EGT). Expression of GFP was determined using a fluorescent microscope and flow cytometry and expression of luciferase by measuring its activity using a luminometer. The EGT protocol yielded the highest expression of both reporter genes. However, a careful optimization of combinations of HV and LV pulses may result in similar transfection as EGT pulses. With the combination protocol, relatively high fields of LV pulses were necessary to obtain comparable transfection to the EGT protocol. Expression of reporter genes was higher in B16 melanoma than in SA-1 fibrosarcoma. Our data support the hypothesis that both electropermeabilization and electrophoresis are involved in electrotransfer of plasmid DNA, but demonstrate that these components have to happen at the same time to obtain significant expression of the target gene in tumors.

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“…4,6 There have been numerous reviews of the advantages and disadvantages of various models of cancer vaccine, therapeutic versus prophylactic vaccines and transplantable versus autochthonous tumors 7 as well as the current tools such as adjuvants that have been used to enhance the immune responses generated by the vaccines. 8 Furthermore, there has been a recent surge in interest in using electroporation to enhance the delivery of plasmids or drugs with anti-tumor effects, as reviewed by Gothelf et al 9 and Heller et al 10 Female BALB/c mice transgenic for the transforming rat neu 664VÀE oncogenes (BALB-neuT 664VÀE mice) display p185 neu , the protein product of rat neu oncogene, on the surface of the cells of their rudimentary mammary glands at 3 weeks of age. As a natural consequence of p185 neu overexpression and signal transduction, foci of atypical hyperplasia appear first in the terminal buds and then as lateral buds sprouting from ducts and ductules in all the 10 glands.…”

Section: Introductionmentioning

confidence: 99%

DNA immunization using constant-current electroporation affords long-term protection from autochthonous mammary carcinomas in cancer-prone transgenic mice

Curcio

Khan²,

Amici

et al. 2007

Cancer Gene Ther

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A recently developed, adaptive constant-current electroporation technique was used to immunize mice with an intramuscular injection of plasmid coding for the extracellular and transmembrane domains of the product of the rat neu 664V-E oncogene protein.In wild-type BALB/c mice, plasmid electroporation at lower current settings elicits higher antibody titers, a strong cytotoxic response and completely protects all mice vaccinated with 10, 25 and 50 mg of plasmid against a lethal challenge of rat neu þ carcinoma cells. BALB/c mice transgenic for the transforming rat neu 664VÀE (ErbB-2, Her-2/neu) oncogene (BALB-neuT 664VÀE ) develop an invasive mammary gland carcinoma by 20 weeks of age. Remarkably, when transgenic BALB-neuT 664VÀE mice were vaccinated at a 10-week interval with 50 mg of plasmid with 0.2 A electroporation, mice remained tumor free for more than a year. A single administration of plasmid associated with electroporation was enough to markedly delay carcinogenesis progression in mice with multiple microscopic invasive carcinomas, and keep about 50% of mice tumor free at one year of age. Thus, vaccination using a clinically relevant dose of plasmid encoding the extracellular and transmembrane domains of the neu oncogene delivered by electroporation prevents long-term tumor formation. These improvements in the efficacy of this cancer vaccine regimen vastly increase its chances for clinical success.

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In VivoElectroporation for Gene Therapy

Cited by 211 publications

References 88 publications

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

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

Control by pulse parameters of DNA electrotransfer into solid tumors in mice

DNA immunization using constant-current electroporation affords long-term protection from autochthonous mammary carcinomas in cancer-prone transgenic mice

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