Enhanced in vivo transgene expression and immunogenicity from plasmid vectors following electrostimulation in rodents and primates

Abstract Safe and efficient methods for in vivo delivery of transgenes of interest must be developed so that the promise of these therapies can be practically used in the clinic. In this work, we describe the use of electrostimulation to enhance the in vivo efficiency of plasmid DNA delivery. The me...

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Veröffentlicht in:Vaccine 2008-09, Vol.26 (40), p.5202-5209
Hauptverfasser: Simon, Adam J, Casimiro, Danilo R, Finnefrock, Adam C, Davies, Mary-Ellen, Tang, Aimin, Chen, Minchun, Chastain, Michael, Kath, Gary S, Chen, Ling, Shiver, John W
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container_end_page 5209
container_issue 40
container_start_page 5202
container_title Vaccine
container_volume 26
creator Simon, Adam J
Casimiro, Danilo R
Finnefrock, Adam C
Davies, Mary-Ellen
Tang, Aimin
Chen, Minchun
Chastain, Michael
Kath, Gary S
Chen, Ling
Shiver, John W
description Abstract Safe and efficient methods for in vivo delivery of transgenes of interest must be developed so that the promise of these therapies can be practically used in the clinic. In this work, we describe the use of electrostimulation to enhance the in vivo efficiency of plasmid DNA delivery. The method was optimized to work over a range of moderate frequencies, utilizing low field strengths and simple symmetrical waveforms. After studying several parameters of delivery in mice, we demonstrate how this methodology can be employed to significantly improve both gene expression (over 16-fold) and the immunogenicity of HIV-1 vaccines (over 28-fold) compared to naked DNA in non-human primates. Compared to an efficient viral Ad5 vector system, the gene expression levels of DNA + electrostimulation were surprisingly within a factor of four of the viral delivery system.
doi_str_mv 10.1016/j.vaccine.2008.03.058
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source MEDLINE; Elsevier ScienceDirect Journals
subjects AIDS Vaccines - genetics
AIDS Vaccines - immunology
Alkaline Phosphatase - genetics
Allergy and Immunology
Animals
Applied microbiology
Biological and medical sciences
Cell Line
DNA vaccines
Electroporation
Electroporation - methods
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene Transfer Techniques
Genetic Vectors
HIV Infections - immunology
HIV Infections - prevention & control
Human immunodeficiency virus 1
Humans
Macaca
Mice
Mice, Inbred BALB C
Microbiology
Plasmids - genetics
Primates
Transgenes
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, DNA - genetics
Vaccines, DNA - immunology
title Enhanced in vivo transgene expression and immunogenicity from plasmid vectors following electrostimulation in rodents and primates
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