Duration and level of transgene expression after gene electrotransfer to skin in mice

Gothelf, Anita; Eriksen, Jens; Højman, Pernille; Gehl, Julie

doi:10.1038/gt.2010.35

Cited by 43 publications

(31 citation statements)

References 44 publications

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“…This can be expected as in comparison with muscle cells, epidermal and dermal cells divide much more frequently and are a subject to constant cell death and desquamation, in the case of keratinocytes. 24 Another rationale for higher protein expression in muscle tissue might be an enhanced susceptibility of this anatomical location to the in vivo transfection. Injection of fluid into the muscle and skin results in different outcome in terms of its distribution.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging

Petkov

Heuts

Krotova

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Discussionmentioning

confidence: 99%

Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging

Petkov

Heuts

Krotova

et al. 2013

Human Vaccines & Immunotherapeutics

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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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“…Besides gene optimization and the use of adjuvants (17), the most promising approach for plasmid vaccines administered as a single modality is by the use of in vivo electroporation (EP). EP has been shown to considerably increase the transfection efficacy of plasmid vaccines, ultimately leading to enhanced and long-lasting expression (10,24) and improved immunogenicity (13,21,27,28) of the encoded antigen. Furthermore, the electric pulses cause mild inflammation, with resulting recruitment of antigen-presenting cells (APCs) to the site of injection (19,24), which further enhances the immunogenicity.…”

mentioning

confidence: 99%

Comparison of Plasmid Vaccine Immunization Schedules Using IntradermalIn VivoElectroporation

Holzmann

Hallermalm

Maltais³

et al. 2011

Clin. Vaccine Immunol.

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In vivo electroporation (EP) has proven to significantly increase plasmid transfection efficiency and to augment immune responses after immunization with plasmids. In this study, we attempted to establish an immunization protocol using intradermal (i. Vaccination with genes was first described in the early 1990s and is becoming an alternative to traditional vaccine strategies. DNA vaccines possess several advantages, such as the capacity to induce a balanced immune response including humoral as well as cellular immune responses similar to those induced during natural infection with intracellular pathogens. The potential of DNA vaccines has been shown in numerous preclinical studies and by the licensure of veterinary DNA vaccines against infectious diseases and cancer (3,9,20). However, immunogenicity has been limited in humans, and ways to enhance the potency of these vaccines are being investigated. Besides gene optimization and the use of adjuvants (17), the most promising approach for plasmid vaccines administered as a single modality is by the use of in vivo electroporation (EP). EP has been shown to considerably increase the transfection efficacy of plasmid vaccines, ultimately leading to enhanced and long-lasting expression (10, 24) and improved immunogenicity (13, 21, 27, 28) of the encoded antigen. Furthermore, the electric pulses cause mild inflammation, with resulting recruitment of antigen-presenting cells (APCs) to the site of injection (19,24), which further enhances the immunogenicity.dAlthough intramuscular (i.m.) delivery of DNA vaccines, with or without the addition of EP, has been studied most extensively, DNA vaccine delivery to skin is becoming increasingly popular. Unlike muscle tissue, the dermal tissue has a large population of resident APCs, including Langerhans cells and dermal dendritic cells, that can facilitate the induction of vaccine-specific immune responses (2, 16). There is also a more rapid turnover of cells in the skin than in muscle, which together with the large number of APCs can lead to a rather fast removal of plasmids from the site of injection (24). This feature is positive for vaccination, as transient expression of the encoded antigen is sufficient to induce strong immune responses. The rapid removal of vaccine plasmids might also explain why more DNA is usually required to induce the same level of expression as that induced by i.m. delivery (10, 15). The skin is also an assessable tissue, making both monitoring and evaluation of immune responses easy to perform. More importantly, the addition of EP after intradermal (i.d.) delivery appears safe, as it does not affect the persistence or integration of vaccine plasmids (5, 24).Laddy et al. conducted a head-to-head comparison of EP-augmented i.m. and i.d. delivery of equal amounts of influenza virus-encoding vaccine plasmids in rhesus macaques. Immune reactivity assessed after three immunizations revealed that i.m. EP induced the highest levels of cellular immune responses, whereas i.d. EP was superior for induction of c...

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Duration and level of transgene expression after gene electrotransfer to skin in mice

Cited by 43 publications

References 44 publications

Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging

Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging

Preclinical Validation of Electrochemotherapy as an Effective Treatment for Brain Tumors

Comparison of Plasmid Vaccine Immunization Schedules Using IntradermalIn VivoElectroporation

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