title: Improved hepatic gene transfer by using an adeno-associated virus serotype 5 vector.
abstract: Adeno-associated viral (AAV) vectors have been shown to direct stable gene transfer and expression in hepatocytes, which makes them attractive tools for treatment of inherited disorders such as hemophilia B. While substantial levels of coagulation factor IX (F.IX) have been achieved using AAV serotype 2 vectors, use of a serotype 5 vector further improves transduction efficiency and levels of F.IX transgene expression by 3- to 10-fold. In addition, the AAV-5 vector transduces a higher proportion of hepatocytes ( approximately 15%). The subpopulations of hepatocytes transduced with either vector widely overlap, with the AAV-5 vector transducing additional hepatocytes and showing a wider area of transgene expression throughout the liver parenchyma.
authors.affiliation: Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Mingozzi
authors.forename: Jörg
authors.initials: J
authors.lastname: Schüttrumpf
authors.forename: Valder R
authors.initials: VR
authors.lastname: Arruda
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Liu
authors.forename: Katherine A
authors.initials: KA
authors.lastname: High
authors.forename: Weidong
authors.initials: W
authors.lastname: Xiao
authors.forename: Roland W
authors.initials: RW
authors.lastname: Herzog
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics / Q000502:physiology*; D005164:Factor IX / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology*; D002836:Hemophilia B / Q000628:therapy; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D005164:Factor IX