Adipose tissue: a new target for electroporation-enhanced DNA vaccines

Fisher, Paul D.; Brambila, C J; McCoy, Jay R.; Kiosses, William B.; Mendoza, Janess; Oh, Janet; Yung, Bryan S.; Schultheis, Katherine; Smith, Trevor R.F.; Broderick, Kate E.

doi:10.1038/gt.2017.96

Cited by 13 publications

(9 citation statements)

References 48 publications

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“…This supports a conclusion where the expression due to GET after ID injection of the plasma is mostly present in the hypodermis and in the fatty tissues. The adipocytes were recently shown to be a target for GET in the skin 58 .…”

Section: Discussionmentioning

confidence: 99%

Safe and efficient novel approach for non-invasive gene electrotransfer to skin

Pasquet

Chabot

Bellard

et al. 2018

Sci Rep

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Gene transfer into cells or tissue by application of electric pulses (i.e. gene electrotransfer (GET)) is a non-viral gene delivery method that is becoming increasingly attractive for clinical applications. In order to make GET progress to wide clinical usage its efficacy needs to be improved and the safety of the method has to be confirmed. Therefore, the aim of our study was to increase GET efficacy in skin, by optimizing electric pulse parameters and the design of electrodes. We evaluated the safety of our novel approach by assaying the thermal stress effect of GET conditions and the biodistribution of a cytokine expressing plasmid. Transfection efficacy of different pulse parameters was determined using two reporter genes encoding for the green fluorescent protein (GFP) and the tdTomato fluorescent protein, respectively. GET was performed using non-invasive contact electrodes immediately after intradermal injection of plasmid DNA into mouse skin. Fluorescence imaging of transfected skin showed that a sophistication in the pulse parameters could be selected to get greater transfection efficacy in comparison to the standard ones. Delivery of electric pulses only mildly induced expression of the heat shock protein Hsp70 in a luminescent reporting transgenic mouse model, demonstrating that there were no drastic stress effects. The plasmid was not detected in other organs and was found only at the site of treatment for a limited period of time. In conclusion, we set up a novel approach for GET combining new electric field parameters with high voltage short pulses and medium voltage long pulses using contact electrodes, to obtain a high expression of both fluorescent reporter and therapeutic genes while showing full safety in living animals.

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Section: Discussionmentioning

confidence: 99%

Safe and efficient novel approach for non-invasive gene electrotransfer to skin

Pasquet

Chabot

Bellard

et al. 2018

Sci Rep

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“…Initially, groups of mice were immunized three times, two weeks apart, with 25 μg of either scMAYV-E or an pVax1 empty vector plasmid using EP-enhanced intramuscular (i.m.) delivery [31]. Immunized mice were bled on day 0 and one week after each injection to obtain sera, which were assayed for the presence of antibodies to MAYV envelope using ELISA with commercially available MAYV E1 and E2 glycoproteins.…”

Section: Resultsmentioning

confidence: 99%

Protective immunity by an engineered DNA vaccine for Mayaro virus

et al. 2019

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Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.

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“…In this regard, Granneman et al [167] performed plasmid DNA electrotransfer in mature fat tissue cells with a selectivity over 99%-the technique was named "adiporation". Fisher et al [168] used the "adiporation" technique in order to perform DNA vaccines in a noninvasive approach by using plate electrodes. Their hypothesis was that these electrodes will efficiently concentrate the electric field within the interscapular subcutaneous adipose tissue of guinea pigs.…”

Section: Adipose Cells' Loading Strategiesmentioning

confidence: 99%

Adipocyte-Based Cell Therapy in Oncology: The Role of Cancer-Associated Adipocytes and Their Reinterpretation as Delivery Platforms

et al. 2020

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Cancer-associated adipocytes have functional roles in tumor development through secreted adipocyte-derived factors and exosomes and also through metabolic symbiosis, where the malignant cells take up the lactate, fatty acids and glutamine produced by the neighboring adipocytes. Recent research has demonstrated the value of adipocytes as cell-based delivery platforms for drugs (or prodrugs), nucleic acids or loaded nanoparticles for cancer therapy. This strategy takes advantage of the biocompatibility of the delivery system, its ability to locate the tumor site and also the predisposition of cancer cells to come in functional contact with the adipocytes from the tumor microenvironment for metabolic sustenance. Also, their exosomal content can be used in the context of cancer stem cell reprogramming or as a delivery vehicle for different cargos, like non-coding nucleic acids. Moreover, the process of adipocytes isolation, processing and charging is quite straightforward, with minimal economical expenses. The present review comprehensively presents the role of adipocytes in cancer (in the context of obese and non-obese individuals), the main methods for isolation and characterization and also the current therapeutic applications of these cells as delivery platforms in the oncology sector.

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Adipose tissue: a new target for electroporation-enhanced DNA vaccines

Cited by 13 publications

References 48 publications

Safe and efficient novel approach for non-invasive gene electrotransfer to skin

Safe and efficient novel approach for non-invasive gene electrotransfer to skin

Protective immunity by an engineered DNA vaccine for Mayaro virus

Adipocyte-Based Cell Therapy in Oncology: The Role of Cancer-Associated Adipocytes and Their Reinterpretation as Delivery Platforms

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