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1.
Bioelectrochemistry ; 144: 107994, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1499650

ABSTRACT

Gene therapies are revolutionizing medicine by providing a way to cure hitherto incurable diseases. The scientific and technological advances have enabled the first gene therapies to become clinically approved. In addition, with the ongoing COVID-19 pandemic, we are witnessing record speeds in the development and distribution of gene-based vaccines. For gene therapy to take effect, the therapeutic nucleic acids (RNA or DNA) need to overcome several barriers before they can execute their function of producing a protein or silencing a defective or overexpressing gene. This includes the barriers of the interstitium, the cell membrane, the cytoplasmic barriers and (in case of DNA) the nuclear envelope. Gene electrotransfer (GET), i.e., transfection by means of pulsed electric fields, is a non-viral technique that can overcome these barriers in a safe and effective manner. GET has reached the clinical stage of investigations where it is currently being evaluated for its therapeutic benefits across a wide variety of indications. In this review, we formalize our current understanding of GET from a biophysical perspective and critically discuss the mechanisms by which electric field can aid in overcoming the barriers. We also identify the gaps in knowledge that are hindering optimization of GET in vivo.


Subject(s)
Electroporation , Gene Transfer Techniques , Genetic Therapy , Animals , COVID-19/prevention & control , Electroporation/instrumentation , Electroporation/methods , Equipment Design , Gene Transfer Techniques/instrumentation , Genetic Therapy/methods , Humans , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , Vaccines, DNA/therapeutic use , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/therapeutic use , /genetics , /therapeutic use
2.
Proc Natl Acad Sci U S A ; 118(45)2021 11 09.
Article in English | MEDLINE | ID: covidwho-1475573

ABSTRACT

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array ("ePatch") for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin's epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , Electroporation/instrumentation , SARS-CoV-2 , Vaccines, DNA/administration & dosage , Animals , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Costs and Cost Analysis , Electroporation/economics , Electroporation/methods , Equipment Design , Female , Genes, Reporter , Humans , Mice , Mice, Inbred BALB C , Microelectrodes , Needles , Pandemics/prevention & control , Proof of Concept Study , Rats , Rats, Wistar , Skin/immunology , Skin/metabolism , Transfection , Vaccination/economics , Vaccination/instrumentation , Vaccination/methods , Vaccines, DNA/genetics , Vaccines, DNA/immunology
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