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Genetic Vaccines and Therapy

, 6:16

First Online: 04 December 2008Received: 14 July 2008Accepted: 04 December 2008

Abstract

BackgroundElectroporation is an established technique for enhancing plasmid delivery to many tissues in vivo, including the skin. We have previously demonstrated efficient delivery of plasmid DNA to the skin utilizing a custom-built four-plate electrode. The experiments described here further evaluate cutaneous plasmid delivery using in vivo electroporation. Plasmid expression levels are compared to those after liposome mediated delivery.

MethodsEnhanced electrically-mediated delivery, and less extensively, liposome complexed delivery, of a plasmid encoding the reporter luciferase was tested in rodent skin. Expression kinetics and tissue damage were explored as well as testing in a second rodent model.

ResultsExperiments confirm that electroporation alone is more effective in enhancing reporter gene expression than plasmid injection alone, plasmid conjugation with liposomes followed by injection, or than the combination of liposomes and electroporation. However, with two time courses of multiple electrically-mediated plasmid deliveries, neither the levels nor duration of transgene expression are significantly increased. Tissue damage may increase following a second treatment, no further damage is observed after a third treatment. When electroporation conditions utilized in a mouse model are tested in thicker rat skin, only higher field strengths or longer pulses were as effective in plasmid delivery.

ConclusionElectroporation enhances reporter plasmid delivery to the skin to a greater extent than the liposome conjugation method tested. Multiple deliveries do not necessarily result in higher or longer term expression. In addition, some impact on tissue integrity with respect to surface damage is observed. Pulsing conditions should be optimized for the model and for the expression profile desired.

AbbreviationsDNAdeoxyribonucleic acid, or gWizLuc specifically in Tables 1 and 2

EPelectroporation

4PEfour-plate electrode

DOTAPN-1-2,3-dioleoyloxy propyl-N,N,N-trimethyl-ammonium-methyl-sulfate.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-0556-6-16 contains supplementary material, which is available to authorized users.

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Autor: Loree C Heller - Mark J Jaroszeski - Domenico Coppola - Richard Heller

Fuente: https://link.springer.com/







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