Journal article
Ultrasound-Guided Gene Transfer to Hepatocytes in utero
Fetal diagnosis and therapy, Vol.13(4), pp.197-205
08/1998
DOI: 10.1159/000020838
PMID: 9784638
Abstract
Objectives: Several inherited liver diseases are associated with a progressive course that begins early in life. Such disorders may be amenable to treatment with gene transfer in the fetal or neonatal period. Methods: We used ultrasound guidance to deliver an adenoviral vector to the liver of 28-day gestation fetal rabbits by cardiocentesis. β-Galactosidase reporter gene expression in hepatocytes was analyzed 3, 7, and 21 days after vector delivery. Using this nonsurgical approach, the viral vector was efficiently delivered into the fetal circulation. Results: The liver was the main organ targeted by this route of administration with up to 40% of the hepatocytes β-galactosidase positive in some animals. The β-galactosidase expression in hepatocytes gradually declined between 3 and 21 days following gene transfer. Associated with the decline in gene expression, an increased number of inflammatory cells were noted in the livers of adenoviral vector treated animals. This suggests that an immune response limits the duration of gene expression in the fetal rabbit, similar to the findings in postnatal animals. Conclusions: This animal model and vector delivery method may be useful for evaluating gene transfer to the fetus with viral and nonviral vectors. Further modifications of the adenoviral vector to reduce immunogenicity may enhance the duration of expression.
Details
- Title: Subtitle
- Ultrasound-Guided Gene Transfer to Hepatocytes in utero
- Creators
- Guoshun WangRoger WilliamsonGlenda MuellerPatricia ThomasBeverly L DavidsonPaul B McCray Jr
- Resource Type
- Journal article
- Publication Details
- Fetal diagnosis and therapy, Vol.13(4), pp.197-205
- DOI
- 10.1159/000020838
- PMID
- 9784638
- ISSN
- 1015-3837
- eISSN
- 1421-9964
- Number of pages
- 9
- Language
- English
- Date published
- 08/1998
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Obstetrics and Gynecology; Internal Medicine
- Record Identifier
- 9984093490902771
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