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• W2155341692 abstract "Several groups including our own have reported gene delivery to fetal organs by vector administration into the amniotic cavity. Based on these studies we hypothesised that the large surface of the fetal skin may be exploitable for high level production of systemically required gene products to be released into the fetal circulation.We administered E1/E3-deleted adenoviral vectors carrying a bacterial beta-galactosidase gene or the human coagulation factor IX gene into the amniotic cavities of mid- to late-gestation mouse fetuses. The concentrations of human factor IX in the plasma of fetal or new-born mice were determined by ELISA. Reverse transcription PCR was used to identify sites of transgene expression.Application of 5 x 10(8) infectious units of the factor IX gene vector in utero resulted in plasma concentrations of human factor IX of up to 1.2 microg/ml without significant decrease in fetal survival. Transgenic protein was found to be produced in the fetal skin, mucosae and amniotic membranes and was shown to be present for several days after birth of healthy pups.As ultrasound-guided amniocentesis in humans is a well-established diagnostic procedure, delivery of the factor IX gene into the amniotic cavity appears to be a safe route for prenatal treatment of haemophilia B and may prevent haemorrhagic complications such as intracranial bleeding during delivery. Our study allowed for the first time a quantification of the expression of a potentially therapeutic transgene in rodents after prenatal gene delivery. It thus provides a model for the prenatal treatment of haemophilia B, but may also serve as a pathfinder to gene therapy of inheritable skin disorders such as epidermolysis bullosa." @default.
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• W2155341692 date "1999-11-01" @default.
• W2155341692 modified "2023-09-24" @default.
• W2155341692 title "Therapeutic plasma concentrations of human factor IX in mice after gene delivery into the amniotic cavity: a model for the prenatal treatment of haemophilia B" @default.
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• W2155341692 doi "https://doi.org/10.1002/(sici)1521-2254(199911/12)1:6<424::aid-jgm70>3.0.co;2-q" @default.
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