title: A hexon-specific PEGylated adenovirus vector utilizing blood coagulation factor X.
abstract: We previously developed a hexon-specific PEGylated adenovirus (Ad) vector by utilizing avidin-biotin interaction. However, the Ad vector was aggregated due to the multiple interactions between avidin and biotin, resulting in a reduction in the transduction efficiencies in the organs following systemic administration. In this study, we developed a new method for hexon-specific PEGylation by mixing Ad vectors with PEGylated blood coagulation factor X (FX) (PEG-FX). FX specifically binds to the hexon protein, suggesting that FX serves as an adaptor molecule for hexon-specific modification. Intravenous administration of the PEG-FX-associated Ad (PEG-FX-Ad) vector into conventional mice resulted in prolonged blood retention. However, the transduction efficiencies in the liver were not reduced by PEG-FX. On the other hand, in the warfarinized mice, the PEG-FX-Ad vectors exhibited a significant reduction in the liver transduction. In addition, incubation of the PEG-FX-Ad vector with unmodified FX resulted in dissociation of PEG-FX from the Ad vector, indicating that a substitution of PEG-FX with endogenous FX occurs in the blood following administration. This study demonstrates that FX can be used as an adaptor molecule for hexon-specific modification; however, modified FX might be substituted with endogenous FX in the blood.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Matsui
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Katayama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Sayuri
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kohdai
authors.initials: K
authors.lastname: Takahira
authors.forename: Masashi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000737:chemistry; D036022:Capsid Proteins / Q000235:genetics*; D002460:Cell Line; D005170:Factor X / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D014018:Tissue Distribution; D014161:Transduction, Genetic; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D036022:Capsid Proteins; D011994:Recombinant Proteins; C018315:hexon capsid protein, Adenovirus; D011092:Polyethylene Glycols; D014859:Warfarin; D005170:Factor X