title: Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery.
abstract: This study describes a multifunctional envelope-type nano device (MEND) that mimics an envelope-type virus based on a novel packaging strategy. MEND particles contain a DNA core packaged into a lipid envelope modified with an octaarginine peptide. The peptide mediates internalization via macropinocytosis, which avoids lysosomal degradation. MEND-mediated transfection of a luciferase expression plasmid achieved comparable efficiency to adenovirus-mediated transfection, with lower associated cytotoxicity. Furthermore, topical application of MEND particles containing constitutively active bone morphogenetic protein (BMP) type IA receptor (caBmpr1a) gene had a significant impact on hair growth in vivo. These data demonstrate that MEND is a promising non-viral gene delivery system that may provide superior results to existing non-viral gene delivery technologies.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: I A
authors.initials: IA
authors.lastname: Khalil
authors.forename: K
authors.initials: K
authors.lastname: Kogure
authors.forename: S
authors.initials: S
authors.lastname: Futaki
authors.forename: S
authors.initials: S
authors.lastname: Hama
authors.forename: H
authors.initials: H
authors.lastname: Akita
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: H
authors.initials: H
authors.lastname: Kishida
authors.forename: M
authors.initials: M
authors.lastname: Kudoh
authors.forename: Y
authors.initials: Y
authors.lastname: Mishina
authors.forename: K
authors.initials: K
authors.lastname: Kataoka
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009842:Oligopeptides / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000821:virology; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: D009842:Oligopeptides; C448619:octaarginine; D008156:Luciferases; D001616:beta-Galactosidase