title: In vivo stable transduction of humanized liver tissue in chimeric mice via high-capacity adenovirus-lentivirus hybrid vector.
abstract: We developed hybrid vectors employing high-capacity adenovirus as a first-stage carrier encoding all the components required for in situ production of a second-stage lentivirus, thereby achieving stable transgene expression in secondary target cells. Such vectors have never previously been tested in normal tissues, because of the scarcity of suitable in vivo systems permissive for second-stage lentivirus assembly. Here we employed a novel murine model in which endogenous liver tissue is extensively reconstituted with engrafted human hepatocytes, and successfully achieved stable transduction by the second-stage lentivirus produced in situ from first-stage adenovirus. This represents the first demonstration of the functionality of adenoviral-lentiviral hybrid vectors in a normal parenchymal organ in vivo.
authors.affiliation: Division of Digestive Diseases, Department of Medicine, University of California at Los Angeles , Los Angeles, CA 90095, USA. s-kubo@hyo-med.ac.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Kubo
authors.forename: Miho
authors.initials: M
authors.lastname: Kataoka
authors.forename: Chise
authors.initials: C
authors.lastname: Tateno
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Faure-Kumar
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Palmer
authors.forename: Philip
authors.initials: P
authors.lastname: Ng
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasahara
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002678:Chimera / Q000378:metabolism* / Q000821:virology; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D007275:Injections, Intravenous; D016086:Lentivirus / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D014161:Transduction, Genetic / Q000379:methods*