Characterization of in vitro and in vivo gene transfer properties of adenovirus serotype 35 vector.
We have recently developed a replication-defective, recombinant adenovirus (Ad) vector composed of the whole Ad serotype 35 (Ad35), a member of subgroup B. We describe herein the in vitro and in vivo gene transfer properties of Ad35 vector in comparison with Ad serotype 5 (Ad5) and the Ad5F35 vector, which is a fiber-substituted Ad5 vector containing Ad35 fiber proteins. In vitro, Ad35 vector efficiently transduced not only human CAR-positive cells but also CAR-negative cells. Following intravenous administration into mice, both Ad5 and Ad35 vectors were rapidly cleared from the bloodstream with a half-life of approximately 3 min. Ad5 vector-mediated transgene expression predominantly occurred in liver parenchymal cells, although the Ad5 vector was delivered to both liver parenchymal and nonparenchymal cells. In contrast, Ad35 vector was efficiently taken up by liver nonparenchymal cells and mediated transduction efficiency in the liver on a level 4 log orders lower than the Ad5 vector. These findings demonstrate that Ad35 vector is an attractive vehicle for gene transfer into human cells, while the biodistribution profile of Ad35 vector in mice is much different from that of the Ad5 vector.
Sakurai
Fuminori
F
Division of Cellular and Gene Therapy Products, 158-8501, Tokyo, Japan.
Mizuguchi
Hiroyuki
H
Yamaguchi
Teruhide
T
Hayakawa
Takao
T
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D020014:K562 Cells; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D016133:Polymerase Chain Reaction; D013997:Time Factors; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics; D020298:U937 Cells
D008156:Luciferases