title: Enhanced in vivo gene transfer into the placenta using RGD fiber-mutant adenovirus vector.
abstract: Among viral vectors, the fiber-mutant adenovirus vector carrying the Arg-Gly-Asp (RGD) peptide sequence (Ad-RGD) seems to have potential for both clinical gene therapy and basic research. As a part of a thorough evaluation of Ad-RGD in preclinical studies, we designed an experiment to investigate in detail the distribution of Ad-RGD compared with conventional adenovirus vector (WT-Ad) in pregnant mice. Surprisingly, Ad-RGD had substantial placental tropism, at 10-100 times that of WT-Ad. Transgene expression was sustained for at least 7 days, and Ad-RGD expressing firefly luciferase or red fluorescent protein has so far caused no placental dysfunction leading to fetal death. Ad-RGD showed high levels of transduction efficiency in in vitro-differentiated trophoblast stem cells, in which higher expression of αvβ3 integrin than in undifferentiated cells was observed. Our results suggest that the use of Ad-RGD or another RGD-mediated targeting strategy holds promise for drug delivery to the placenta.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Katayama
authors.forename: Rie
authors.initials: R
authors.lastname: Furuki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneko
authors.forename: Masashi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshida
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Nagase
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakanishi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013234:Stem Cells / Q000378:metabolism; D019076:Transgenes; D014327:Trophoblasts / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D039302:Integrin alphaVbeta3; D008164:Luminescent Proteins; D009842:Oligopeptides; D000097573:Red Fluorescent Protein; C047981:arginyl-glycyl-aspartic acid