title: Enhanced gene expression promoted by the quantized folding of pDNA within polyplex micelles.
abstract: Selective packaging of plasmid DNA (pDNA) into folded rod or collapsed sphere structures in polyplex micelles was demonstrated by modulating the PLys segment length of poly(ethylene glycol)-block- poly(L-lysine) (PEG-PLys) block catiomers used for micelle formation. The two basic packaging structures correlated well to the integrity of double-stranded DNA contained within the micelles. Rod structures formed by the quantized folding mechanism, which results in dissociation of double-stranded DNA only at each fold. Collapsed sphere structures formed by substantial random disruption of the double-stranded DNA structure. Analysis of gene expression in a cell-free transcription/translation system, cultured cells and also skeletal muscle of mice showed that micelles containing pDNA packaged by quantized folding exhibited higher gene expression than naked pDNA and micelles containing collapsed pDNA. These results indicate that controlled packaging of pDNA into an appropriate structure is critical for achieving effective gene expression. Improved gene transfection and expression resulting from the quantized folding of pDNA within polyplex micelles is promising for application in therapeutic gene delivery systems.
authors: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Kensuke
authors: K
authors: Osada
authors: Tomonori
authors: T
authors: Shiotani
authors: Theofilus A
authors: TA
authors: Tockary
authors: Daigo
authors: D
authors: Kobayashi
authors: Hiroki
authors: H
authors: Oshima
authors: Sorato
authors: S
authors: Ikeda
authors: Ronald J
authors: RJ
authors: Christie
authors: Keiji
authors: K
authors: Itaka
authors: Kazunori
authors: K
authors: Kataoka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008823:Micelles; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000737:chemistry* / Q000235:genetics*
chemical_list: D008823:Micelles; D004247:DNA