Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation

Vaccines
Janess M MendozaKate E Broderick

Abstract

The skin is an attractive tissue for vaccination in a clinical setting due to the accessibility of the target, the ease of monitoring and most importantly the immune competent nature of the dermal tissue. While skin electroporation offers an exciting and novel future methodology for the delivery of DNA vaccines in the clinic, little is known about the actual mechanism of the approach and the elucidation of the resulting immune responses. To further understand the mechanism of this platform, the expression kinetics and localization of a reporter plasmid delivered via a surface dermal electroporation (SEP) device as well as the effect that this treatment would have on the resident immune cells in that tissue was investigated. Initially a time course (day 0 to day 21) of enhanced gene delivery with electroporation (EP) was performed to observe the localization of green fluorescent protein (GFP) expression and the kinetics of its appearance as well as clearance. Using gross imaging, GFP expression was not detected on the surface of the skin until 8 h post treatment. However, histological analysis by fluorescent microscopy revealed GFP positive cells as early as 1 h after plasmid delivery and electroporation. Peak GFP expression was...Continue Reading

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Citations

Jun 29, 2018·Human Gene Therapy Methods·Katherine SchultheisKate E Broderick
Oct 19, 2017·Human Vaccines & Immunotherapeutics·Kathleen A CashmanConnie S Schmaljohn
Jan 1, 2014·Molecular Therapy. Methods & Clinical Development·Trevor Rf SmithKate E Broderick
Jul 28, 2018·Chemical Reviews·Martin P StewartKlavs F Jensen

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Methods Mentioned

BETA
transfection
transfect
biopsies
biopsy
confocal microscopy
Fluorescent
fluorescence microscopy
light microscopy

Clinical Trials Mentioned

NCT00859729
NCT01403155
NCT01405885

Software Mentioned

Zen

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