Clinical potential of electroporation for gene therapy and DNA vaccine delivery

Lambricht, Laure; Lopes, Alessandra; Kos, Špela; Serša, Gregor; Préat, Véronique; Vandermeulen, Gaëlle

doi:10.1517/17425247.2016.1121990

Cited by 192 publications

(133 citation statements)

References 78 publications

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“…Currently, multiple commercial devices have proved their effectiveness on in vitro gene transfection and become common apparatuses in biological laboratories . Apart from laboratorial gene transfection, EP has also exhibited its potential for efficient gene‐transfection based therapies, such as DNA vaccine and siRNA delivery, since EP is a physical method, without introducing viral or chemical agents, therefore avoiding corresponding bio‐safety concerns . However, difficulties have yet to be addressed before expanding the application of EP.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Cell Responses to Electroporation, a Classical Gene Delivery Approach

Zhao

et al. 2018

Proteomics

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Electroporation, as an established nonviral technology for breaching cell membrane, has been accepted for the delivery of nucleic acids. Despite satisfactory delivery efficiencies have been achieved on multiple cell kinds by simply exhausting all possible electrical parameters, electroporation is still inefficient, or even invalid, for various kinds of cells. This is largely due to the lack of comprehensive understanding of cell responses to electrical stimulation at biological aspect. Moreover, a systematically investigation of protein variation of electroporated cells is also required for biosafety evaluation before clinically applying electroporation. By employing quantitative proteomic analysis, the biological mechanism of electroporation is explored from the molecular level. The results reveal that electrical stimulations widely influence many biological processes including nucleic acid stabilization, protein synthesis, cytoskeleton dynamic, inflammation, and cell apoptosis. It is found that several antivirus-related processes appeared in the enrichment results. Moreover, SAMD9, a broad spectrum antiviral and antitumor factor, is dramatically downregulated on easy-to-transfect cells while electroporation can not alter SAMD9 expression on hard-to-transfect cells, hinting that electroporation, a pure physical treatment, can induce antivirus-like defensive responses and the altering of SAMD9 can be used to predict the effectiveness of electroporation on transfecting specific kinds of cells.

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Section: Introductionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Cell Responses to Electroporation, a Classical Gene Delivery Approach

Zhao

et al. 2018

Proteomics

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“…202,203 Electroporation is a technique, which allows to transiently increase the permeability of the cell membrane by exposing the cell to an electric field. In conventional electroporation protocols, cells in suspension or in tissue are placed between two electrodes to which a voltage pulse (typically hundreds of ls to tens of ms long) is applied.…”

Section: Using Nanofluidics To Inject Dna Into Living Cellsmentioning

confidence: 99%

Flow of DNA in micro/nanofluidics: From fundamentals to applications

et al. 2016

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Thanks to direct observation and manipulation of DNA in micro/nanofluidic devices, we are now able to elucidate the relationship between the polymer microstructure and its rheological properties, as well as to design new single-molecule platforms for biophysics and biomedicine. This allows exploration of many new mechanisms and phenomena, which were previously unachievable with conventional methods such as bulk rheometry tests. For instance, the field of polymer rheology is at a turning point to relate the complex molecular conformations to the nonlinear viscoelasticity of polymeric fluids (such as coil–stretch transition, shear thinning, and stress overshoot in startup shear). In addition, nanofluidic devices provided a starting point for manipulating single DNA molecules by applying basic principles of polymer physics, which is highly relevant to numerous processes in biosciences. In this article, we review recent progress regarding the flow and deformation of DNA in micro/nanofluidic systems from both fundamental and application perspectives. We particularly focus on advances in the understanding of polymer rheology and identify the emerging research trends and challenges, especially with respect to future applications of nanofluidics in the biomedical field.

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“…Following local injection by needle and syringe plasmid DNA is taken up by a limited number of cells at the site of injection, where the DNA is transcribed into mRNA and translated into antigen intracellularly. Adaptive EP increases the initial uptake of plasmid by local cells approximately 500x [3]. This creates a large antigen bolus to drive a more potent immune response.…”

Section: Introductionmentioning

confidence: 99%

DNA vaccines: prime time is now

Gary

Weiner

2020

Current Opinion in Immunology

133

108

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Recently newer synthetic DNA vaccines have been rapidly advanced to clinical study and have demonstrated an impressive degree of immune potency and tolerability. Improvements in DNA delivery over prior needle and syringe approaches include jet delivery, gene gun delivery, among others. Among the most effective of these new delivery methods, advanced electroporation (EP), combined with other advances, induces robust humoral and cellular immunity in both preventative as well as therapeutic studies. Advancements in the design of the DNA inserts include leader sequence changes, RNA and codon optimizations, improved insert designs, increased concentrations of DNA, and skin delivery, appear to complement newer delivery strategies. These advances also provide a framework for the in vivo production of synthetic DNA biologics. In this review, we focus on recent studies of synthetic DNA vaccines in the clinic for the prevention or treatment of infectious diseases with a focus on adaptive electroporation for delivery, and briefly summarize novel preclinical data advancing the in vivo delivery of DNAencoded antibody-like biologics.

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Clinical potential of electroporation for gene therapy and DNA vaccine delivery

Cited by 192 publications

References 78 publications

Quantitative Proteomic Analysis of Cell Responses to Electroporation, a Classical Gene Delivery Approach

Quantitative Proteomic Analysis of Cell Responses to Electroporation, a Classical Gene Delivery Approach

Flow of DNA in micro/nanofluidics: From fundamentals to applications

DNA vaccines: prime time is now

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