Delivery of plasmid DNA expression vector for keratinocyte growth factor‐1 using electroporation to improve cutaneous wound healing in a septic rat model

Lin, Michael P.; Marti, Guy; Dieb, Rami; Wang, Jiaai; Ferguson, Mark W. J.; Qaiser, Rabia; Bonde, Pramod; Duncan, Mark D.; Harmon, John W.

doi:10.1111/j.1743-6109.2006.00169.x

Cited by 40 publications

(28 citation statements)

References 32 publications

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“…Plasmid DNA of keratinocyte growth factor-1 was transferred to the skin of a septic rat model using electroporation [96], and both the rate and quality of healing were improved. Diabetes also impairs wound healing in elderly patients.…”

Section: Wound Healingmentioning

confidence: 99%

Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances

Murakami

Sunada²

2011

CGT

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Simple plasmid DNA injection is a safe and feasible gene transfer method, but it confers low transfection efficiency and transgene expression. This non-viral gene transfer method is enhanced by physical delivery methods, such as electroporation and the use of a gene gun. In vivo electroporation has been rapidly developed over the last two decades to deliver DNA to various tissues or organs. It is generally considered that membrane permeabilization and DNA electrophoresis play important roles in electro-gene transfer. Skeletal muscle is a well characterized target tissue for electroporation, because it is accessible and allows for long-lasting gene expression ( > one year). Skin is also a target tissue because of its accessibility and immunogenicity. Numerous studies have been performed using in vivo electroporation in animal models of disease. Clinical trials of DNA vaccines and immunotherapy for cancer treatment using in vivo electroporation have been initiated in patients with melanoma and prostate cancer. Furthermore, electroporation has been applied to DNA vaccines for infectious diseases to enhance immunogenicity, and the relevant clinical trials have been initiated. The gene gun approach is also being applied for the delivery of DNA vaccines against infectious diseases to the skin. Here, we review recent advances in the mechanism of in vivo electroporation, and summarize the findings of recent preclinical and clinical studies using this technology.

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Section: Wound Healingmentioning

confidence: 99%

Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances

Murakami

Sunada²

2011

CGT

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“…Several studies regarding gene transfer of vascular endothelial growth factor or keratinocyte growth factor have shown increased wound healing in for example, ischemic skin flaps 41 and septic wounds. 24 Gene transfection to skin has not received the same amount of attention as for example gene transfer to muscle, probably because gene transfer to muscle is efficient and easy to perform. But skin has a number of qualities, which can be valuable in gene therapy.…”

Section: Clinical Relevancementioning

confidence: 99%

“…Up to now gene electrotransfer to skin has been focused on creating a local transfection, either with reporter genes [19][20][21][22] or with the purpose of treating of diabetic or septic wounds. 23,24 Only one study from Maruyama et al 25 has been published using a systemic relevant compound, namely erythropoietin.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice

2010

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Gene electrotransfer refers to gene transfection by electroporation and is an effective non-viral method for delivering naked DNA into cells and tissues. This study presents data from gene electrotransfer with erythropoietin (EPO) to mouse skin. Nine-week-old female NMRI mice received one, two or three intradermal injections of 50 mg EPO plasmid and were subsequently electroporated. With plate electrodes and 100 mg of EPO, a significant increase in hemoglobin (Po0.01) was observed compared with controls. The level of hemoglobin peaked after 5 weeks but stayed significantly elevated for more than 3 months. Serum EPO was significantly increased (Po0.001) 24 h after the transfection and remained significantly different compared with controls until the maximum level of serum EPO was reached after 2 weeks. Eight weeks after the transfection serum EPO returned to baseline. In this study, we have established that gene electrotransfer to skin of even small amounts of DNA can lead to systemically therapeutic levels of protein. This means that in addition to DNA vaccinations, there is a potential utility for electroporation in alleviating systemic diseases such as cancer and protein deficiency disorders.

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“…Its effect is local impairment of collagen synthesis or impairment of the arrival of neutrophils and a failure of optimum keratinocyte repair. Using electrophoresis of a plasmid containing a keratinocyte growth factor, Lin et al [20] achieved a 67% improvement in healing of a skin wound in a rat sepsis model. None of 30 animals died after wounding of the caecum by ligation.…”

Section: Antibioticsmentioning

confidence: 99%