Enhanced in vivo transgene expression and immunogenicity from plasmid vectors following electrostimulation in rodents and primates.
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.
Simon
Adam J
AJ
Department of Alzheimer's Research, Merck Research Laboratories, West Point, PA 19486, USA. adam_simon@merck.com
Casimiro
Danilo R
DR
Finnefrock
Adam C
AC
Davies
Mary-Ellen
ME
Tang
Aimin
A
Chen
Minchun
M
Chastain
Michael
M
Kath
Gary S
GS
Chen
Ling
L
Shiver
John W
JW
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D002460:Cell Line; D018274:Electroporation / Q000379:methods*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D008251:Macaca; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics*; D019076:Transgenes; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D019444:Vaccines, DNA; D000469:Alkaline Phosphatase