title: Electrical enhancement of formulated plasmid delivery in animals.
abstract: 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.
authors.affiliation: Advisys, Inc., 2700 Research Forest Drive, Suite 180, The Woodlands, Texas 77381, USA. ruxandradraghia@advisys.net
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Draghia-Akli
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Cummings
authors.forename: Deena
authors.initials: D
authors.lastname: Parghi
authors.forename: Robert H
authors.initials: RH
authors.lastname: Carpenter
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Brown
mesh_terms: 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
chemical_list: D011099:Polyglutamic Acid; D004247:DNA; D000469:Alkaline Phosphatase