NDLI: Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors.

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Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors.

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Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Koeberl, D. D. Halbert, C. L. Russell, D. W. Miller, A. D. Alexander, I. E.
Description	Author Affiliation: Koeberl DD ( Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.);
Abstract	We previously found that gene transduction by adeno-associated virus (AAV) vectors in cell culture can be stimulated over 100-fold by treatment of the target cells with agents that affect DNA metabolism, such as irradiation or topoisomerase inhibitors. Here we show that previous gamma-irradiation increased the transduction rate in mouse liver by up to 900-fold, and the topoisomerase inhibitor etoposide increased transduction by about 20-fold. Similar rates of hepatic transduction were obtained by direct injection of the liver or by systemic delivery via tail vein injection. Hepatocytes were much more efficiently transduced than other cells after systemic delivery, and up to 3% of all hepatocytes could be transduced after one vector injection. The presence of wild-type AAV, which contaminates many AAV vector preparations, was required to observe a full response to gamma-irradiation. Injection of mice with AAV vectors encoding human clotting factor IX after gamma-irradiation resulted in synthesis of low levels of human clotting factor IX for the 5-month period of observation. These studies show the potential of targeted gene transduction of the liver by AAV vectors for treatment of various hematological or metabolic diseases.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dependovirus Genetics Factor IX Biosynthesis Gene Transfer Techniques Genetic Vectors Liver Metabolism Animals Enzyme Inhibitors Etoposide Pharmacology Gamma Rays Genetic Therapy Injections, Intravenous Virology Mice Recombinant Proteins Topoisomerase I Inhibitors Tumor Cells, Cultured Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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