title: Adenovirus serotype 35 vector-mediated transduction following direct administration into organs of nonhuman primates.
abstract: Adenovirus (Ad) serotype 35 (Ad35) vectors have attracted remarkable attention as alternatives to conventional Ad serotype 5 (Ad5) vectors. In a previous study, we showed that intravenously administered Ad35 vectors exhibited a safer profile than Ad5 vectors in cynomolgus monkeys, which ubiquitously express CD46, an Ad35 receptor, in a pattern similar to that in humans. However, the Ad35 vectors poorly transduced the organs. In this study, we examined the transduction properties of Ad35 vectors after local administration into organs of cynomolgus monkeys. The vectors transduced different types of cells depending on the organ. Hepatocytes and microglia were mainly transduced after the vectors were injected into the liver and cerebrum, respectively. Injection of the vectors into the femoral muscle resulted in the transduction of cells that appeared to be fibroblasts and/or macrophages. Conjunctival epithelial cells showed transgene expression following infusion into the vitreous body of the eyeball. Transgene expression was limited to areas around the injection points in most of the organs. In contrast, Ad35 vector-mediated transgene expression was not detected in any of the organs not injected with Ad35 vectors. These results suggest that Ad35 vectors are suitable for gene delivery by direct administration to organs.
authors.affiliation: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Ibaraki City, Osaka, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Sakurai
authors.forename: S-i
authors.initials: SI
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Akitomo
authors.forename: H
authors.initials: H
authors.lastname: Shibata
authors.forename: K
authors.initials: K
authors.lastname: Terao
authors.forename: K
authors.initials: K
authors.lastname: Kawabata
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: H
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D000256:Adenoviridae / Q000145:classification / Q000235:genetics*; D000287:Administration, Topical; D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D007267:Injections; D008252:Macaca fascicularis; D051916:Membrane Cofactor Protein / Q000378:metabolism; D014018:Tissue Distribution / Q000235:genetics; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051916:Membrane Cofactor Protein; D001616:beta-Galactosidase