title: In vivo gene transfer into muscle via electro-sonoporation.
abstract: Among the nonviral techniques for gene transfer in vivo, electroporation is simple, potent, inexpensive, and safe. To upregulate the expression levels of the transferred gene, we investigated the applicability of in vivo electro-sonoporation, which consists of a combination of electric pulse and ultrasound, for gene transfer using plasmid DNA encoding luciferase and mouse interleukin-12 (mIL-12). The quadriceps muscles of mice were injected with plasmid DNA, then sonoporated for 5 min, and electroporated by a pair of electrode plates at the middle of the duration of sonoporation. Three days later, mice that had undergone electro-sonoporation demonstrated twofold higher luciferase activity and low tissue damage in quadriceps muscle compared to mice having undergone electroporation alone. Serum mIL-12 levels in mice that had undergone electro-sonoporation (peaking at 25.5 ng/ml) were twofold higher after gene transfer than were those in mice having undergone electroporation alone (peaking at 14.3 ng/ml), and maintained high serum level of 13.9 ng/ml at 28 days after gene transfer. The efficacy of gene transfer via electro-sonoporation was superior when the plasmid DNA solution was 0.85% NaCl compared to albumin microbubble echo-contrast material. These results demonstrated that gene transfer into muscle via electro-sonoporation could provide a new potent nonviral technique for gene transfer in vivo.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. yamashi@surg2.med.kyushu-u.ac.jp
authors.forename: Yo-ichi
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tachibana
authors.forename: Norifumi
authors.initials: N
authors.lastname: Harimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Tsujita
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Keizo
authors.initials: K
authors.lastname: Sugimachi
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D018274:Electroporation / Q000379:methods*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D007273:Injections, Intramuscular; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000378:metabolism*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D013997:Time Factors
chemical_list: D005819:Genetic Markers; D018664:Interleukin-12; D004247:DNA; D008156:Luciferases