14 research outputs found

    Costly choices for treating Wilson's disease

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110871/1/hep27663.pd

    Transplant livers in wilson's disease for hepatic, not neurologic, indications

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    No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35274/1/500060522_ftp.pd

    DNA/protein complexes delivered in conjunction with adenovirus generate high-efficiency in vitro transfection: A powerful transfection reagent with potential broad applications

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    We have combined a receptor-mediated DNA delivery system with the endosomal lysis ability of adenovirus and shown that DNA can be delivered into primary hepatocytes, resulting in a high level of gene expression. When asialoorosomucoid conjugated with poly(L-lysine) was used to deliver the Escherichia coli Β-galactosidase gene into primary hepatocytes through binding with the hepatic asialoglycoprotein receptor, only a low level of Β-galactosidase was detectable, with less than 0.1% of the hepatocytes being transfected. This level of activity can be greatly enhanced by the cointernalization of the DNA protein complex with a replication-defective adenovirus, resulting in 100% of the hepatocytes staining blue with 5-bromo-4-chloro-3-indolyI Β-D-galactoside. Quantitative analysis of Β-galactosdase expression also showed a 1000-fold enhancement of activity. To test the applicability of this DNA delivery system for the correction of phenylketonuria, a metabolic disorder that causes severe mental retardation in children, we have delivered the human phenylalanine hydroxylase (PAH) gene to hepatocytes derived from a PAH-deficient mouse strain and dem-onstrated complete reconstitution of enzymatic activity. This method shows great promise for efficient gene delivery to the liver for correction of hepatic disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38404/1/1840180639_ftp.pd
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