Electrical enhancement of formulated plasmid delivery in animals.
Electroporation has been shown to significantly increase plasmid transfer to the skeletal muscle, but this procedure is also implicated in muscle damage. We are reporting a highly efficient in vivo transfer of a plasmid formulated with poly-(L-glutamate) (PLG) into murine, canine and porcine muscle fibers using electric pulses of low field intensity. In mice and pigs, the use of secreted embryonic alkaline phosphatase (SEAP) as the indicator gene caused increased PLG expression by 2-3 fold compared to naked plasmid; while delivery of a PLG-plasmid formulation to dogs showed a 10-fold increase in serum SEAP levels compared to plasmid alone. Muscle lesions were reduced by the protective PLG. Thus, PLG may constitute a useful adjuvant for increased expression and reduced muscle trauma to plasmid DNA delivered by electroporation.
Draghia-Akli
Ruxandra
R
Advisys, Inc., 2700 Research Forest Drive, Suite 180, The Woodlands, Texas 77381, USA. ruxandradraghia@advisys.net
Khan
Amir S
AS
Cummings
Kathleen K
KK
Parghi
Deena
D
Carpenter
Robert H
RH
Brown
Patricia A
PA
D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004247:DNA / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D004622:Embryo, Mammalian / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007273:Injections, Intramuscular; D051379:Mice; D010957:Plasmids / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000378:metabolism; D013552:Swine; D013997:Time Factors
D011099:Polyglutamic Acid; D004247:DNA; D000469:Alkaline Phosphatase