title: Fetal Gene Therapy for Ornithine Transcarbamylase Deficiency by Intrahepatic Plasmid DNA-Micro-Bubble Injection Combined with Hepatic Ultrasound Insonation.
abstract: We evaluated the therapeutic efficacy of hepatic transfection of plasmid DNA using micro-bubbles and ultrasound insonation for fetal correction of ornithine transcarbamylase (OTC) deficiency in mice. Twenty-three sparse-fur heterozygous pregnant mice (day 16 of gestation) were divided into three groups: injection of plasmid-DNA micro-bubble mixture into fetal liver with ultrasound insonation (Tr, n = 11); control group 1 (C1), injection of plasmid-DNA micro-bubble mixture into fetal liver with no insonation (n = 5); and control group 2 (C2), injection of saline-micro-bubble mixture into fetal liver with ultrasound insonation (n = 7). Levels of blood ammonia and urinary orotic acid were significantly lower in the Tr group than in the C1 and C2 groups (p < 0.05, p < 0.01, respectively), whereas OTC activity was not different between groups. Therefore, ultrasound insonation with micro-bubbles enhanced plasmid DNA transfection into fetal mouse liver, leading to one of the therapeutic methods in ammonia metabolism. This might provide more time for OTC-deficient infants until liver transplantation.
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Oishi
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kakimoto
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Wenji
authors.initials: W
authors.lastname: Yuan
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kuno
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan. Electronic address: chiba-t@sea.plala.or.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D008099:Liver; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000196:embryology / Q000628:therapy*; D010957:Plasmids / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods; D014464:Ultrasonic Therapy / Q000379:methods*
keywords: Micro-bubble; OTC deficient mouse; Plasmid DNA; Prenatal gene therapy; Sonotransfection; Ultrasound insonation