In vivo stable transduction of humanized liver tissue in chimeric mice via high-capacity adenovirus-lentivirus hybrid vector.
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.
Kubo
Shuji
S
Division of Digestive Diseases, Department of Medicine, University of California at Los Angeles , Los Angeles, CA 90095, USA. s-kubo@hyo-med.ac.jp
Kataoka
Miho
M
Tateno
Chise
C
Yoshizato
Katsutoshi
K
Kawasaki
Yoshiko
Y
Kimura
Takahiro
T
Faure-Kumar
Emmanuelle
E
Palmer
Donna J
DJ
Ng
Philip
P
Okamura
Haruki
H
Kasahara
Noriyuki
N
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*