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• W2109751467 endingPage "224" @default.
• W2109751467 startingPage "214" @default.
• W2109751467 abstract "ABSTRACT Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to only a small portion of hepatocytes even after administration of extremely high vector doses. In order to investigate whether rAAV vectors of other serotypes exhibit similar restricted liver transduction, we performed a dose-response study by injecting mice with β-galactosidase-expressing rAAV1 and rAAV8 vectors via the portal vein. The rAAV1 vector showed a blunted dose-response similar to that of rAAV2 at high doses, while the rAAV8 vector dose-response remained unchanged at any dose and ultimately could transduce all the hepatocytes at a dose of 7.2 × 10 12 vector genomes/mouse without toxicity. This indicates that all hepatocytes have the ability to process incoming single-stranded vector genomes into duplex DNA. A single tail vein injection of the rAAV8 vector was as efficient as portal vein injection at any dose. In addition, intravascular administration of the rAAV8 vector at a high dose transduced all the skeletal muscles throughout the body, including the diaphragm, the entire cardiac muscle, and substantial numbers of cells in the pancreas, smooth muscles, and brain. Thus, rAAV8 is a robust vector for gene transfer to the liver and provides a promising research tool for delivering genes to various target organs. In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression." @default.
• W2109751467 created "2016-06-24" @default.
• W2109751467 creator A5011138455 @default.
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• W2109751467 date "2005-01-01" @default.
• W2109751467 modified "2023-10-13" @default.
• W2109751467 title "Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice" @default.
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• W2109751467 doi "https://doi.org/10.1128/jvi.79.1.214-224.2005" @default.
• W2109751467 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/538708" @default.
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• W2109751467 hasPublicationYear "2005" @default.
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