Journal of gastroenterology and hepatology · 2010
High volume naked DNA tail-vein injection restores liver function in Fah-knock out mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Eggenhofer Elke, Doenecke Axel, Renner Philipp, Slowik Przemyslaw, Piso Pompiliu, Geissler Edward K, Schlitt Hans J, Dahlke Marc H, Popp Felix C
Аннотация
BACKGROUND: Despite pharmaceutical treatment with NTBC (2-2-nitro-4-fluoromethylbenzoyl-1,3-cyclohexanedione), a high incidence of liver malignancies occur in humans and mice suffering from hereditary tyrosinemia type 1 (HT1) caused by mutation of the fumarylacetoacetate hydrolase (fah) gene.
METHODS: To evaluate the efficacy of a definitive treatment for HT1, we transfected fah knockout mice with naked plasmid DNA using high volume tail-vein injection. This approach was chosen to reduce the occurrence of insertional mutagenesis that is frequently observed when using other (retro-)viral vectors. To prolong gene expression, the fah gene was cloned between adeno-associated virus (AAV)-specific inverted terminal repeats (ITRs).
RESULTS: All animals treated with high volume plasmid DNA injections could be successfully weaned off NTBC and survived in the long term without any further pharmacological support. Up to 50% fah positive hepatocytes were detected in livers of naked plasmid DNA-treated animals and serum liver function tests approximated those of wild-type controls.
CONCLUSIONS: Naked plasmid DNA transfection offers a promising alternative treatment for HT1. Minimizing side-effects makes this approach especially appealing.
METHODS: To evaluate the efficacy of a definitive treatment for HT1, we transfected fah knockout mice with naked plasmid DNA using high volume tail-vein injection. This approach was chosen to reduce the occurrence of insertional mutagenesis that is frequently observed when using other (retro-)viral vectors. To prolong gene expression, the fah gene was cloned between adeno-associated virus (AAV)-specific inverted terminal repeats (ITRs).
RESULTS: All animals treated with high volume plasmid DNA injections could be successfully weaned off NTBC and survived in the long term without any further pharmacological support. Up to 50% fah positive hepatocytes were detected in livers of naked plasmid DNA-treated animals and serum liver function tests approximated those of wild-type controls.
CONCLUSIONS: Naked plasmid DNA transfection offers a promising alternative treatment for HT1. Minimizing side-effects makes this approach especially appealing.
Предметные рубрики MeSH
AnimalsBilirubinBiomarkersCell ProliferationCyclohexanonesDependovirusDisease Models, AnimalGenetic TherapyGenetic VectorsHepatocytesHydrolasesInjections, IntravenousL-Lactate DehydrogenaseLiverLiver Function TestsMiceMice, Inbred BALB CMice, KnockoutNitrobenzoatesPlasmidsSerum AlbuminTailTime FactorsTransfectionTyrosinemiasUrea