Tolerability of Two Sequential Electroporation Treatments Using MedPulser DNA Delivery System (DDS) in Healthy Adults

Wallace, Mark; Evans, Barbara J.; Woods, Sandra J.; Mogg, Robin; Zhang, Lei; Finnefrock, Adam C.; Rabussay, Dietmar; Fons, M.; Mallee, John; Mehrotra, Devan V.; Schödel, Florian; Musey, Luwy

doi:10.1038/mt.2009.27

Cited by 47 publications

(29 citation statements)

References 34 publications

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“…The tolerability of two sequential electroporations using the MedPulser DNA delivery system (DDS) (Inovio, San Diego, CA, USA) was evaluated in 24 healthy adults [121]. Pain severity was assessed based on patient self-reporting using two clinically validated questionnaires: the McGill Pain Questionnaire and the Brief pain Questionnaire.…”

Section: Tolerabilitymentioning

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: Tolerabilitymentioning

confidence: 99%

Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances

Murakami

Sunada²

2011

CGT

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“…2007; Daud et al, 2008;Bodles-Brakhop et al, 2009;Wallace et al, 2009). This becomes an important issue, particularly if it is necessary to treat a large area to obtain therapeutic levels of a delivered transgene.…”

Section: Skin Delivery With Multielectrode Array 359mentioning

confidence: 99%

Electrically Mediated Delivery of Plasmid DNA to the Skin, Using a Multielectrode Array

et al. 2010

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The easy accessibility of skin makes it an excellent target for gene transfer protocols. To take full advantage of skin as a target for gene transfer, it is important to establish an efficient and reproducible delivery system. Electroporation is a strong candidate to meet this delivery criterion. Electroporation of the skin is a simple, direct, in vivo method to deliver genes for therapy. Previously, delivery to the skin was performed by means of applicators with relatively large distances between electrodes, resulting in significant muscle stimulation and pain. These applicators also had limitations in controlling the directionality of the applied field. To resolve this issue, a system consisting of an array of electrodes that decreased the distance between them and that were independently addressable for directional control of the field was developed. This new multielectrode array (MEA) was compared with an established electrode. In a rat model, comparable reporter expression was seen after delivery with each electrode. Delivery was also evaluated in a guinea pig model to determine the potential of this approach in an animal model with skin thickness and structure similar to human skin. The results clearly showed that effective delivery was related to both the electrode and the parameters chosen. With the MEA, the muscle twitching associated with application of electric fields was notably reduced compared with conventional electrode systems. This is important, as it will facilitate the translation of electroporation-mediated gene delivery to skin for clinical use with DNA vaccines or for therapies for cancer or protein deficiencies.

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“…Also, biolistic delivery is hindered by the high sensitivity of the ballistic penetration process to obvious and subtle variation in skin properties [16] and high cell death [17]. The electroporation process causes pain and discomfort to patients [18][19][20].…”

Section: Introductionmentioning

confidence: 99%