title: Modification of pIX or hexon based on fiberless Ad vectors is not effective for targeted Ad vectors.
abstract: Adenovirus (Ad) vector application in gene therapy is limited by its naïve tropism. We previously developed protein IX (pIX)-modified and hexon-modified Ad vectors in order to alter Ad vector tropism. However, these modified Ad vectors failed to infect cells with the foreign ligands displayed in the pIX or hexon. We hypothesized that steric hindrance by fiber proteins might have prevented the ligand-mediated transduction, as fibers are the outmost capsid proteins of Ad vectors. Therefore, we generated a series of fiberless Ad vectors and investigated their gene expression properties. Unexpectively, however, pIX- or hexon-modified fiberless Ad vector did not achieve any gene expression (the gene expression level by these vectors was similar to the background level). These results might be caused by the fact that the fiberless particles were weaker against physical burdens. To the best of our knowledge, this study is the first reported attempt to develop fiberless Ad vectors containing foreign ligands in the pIX or hexon region. The drawback of the lower stability of fiberless Ad vectors must be overcome to develop targeted Ad vectors based on such vectors. This study could provide basic information for the development of effective targeted Ad vectors.
authors.affiliation: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka 567-0085, Japan.
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Kurachi
authors.forename: Naoya
authors.initials: N
authors.lastname: Koizumi
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Tashiro
authors.forename: Haruna
authors.initials: H
authors.lastname: Sakurai
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabata
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D036022:Capsid Proteins / Q000235:genetics*; D002460:Cell Line; D004355:Drug Stability; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D010455:Peptides / Q000235:genetics; D010957:Plasmids; D013696:Temperature; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D036022:Capsid Proteins; D010455:Peptides; C018315:hexon capsid protein, Adenovirus; D008156:Luciferases