title: Poly(ethylene glycol) Crowding as Critical Factor To Determine pDNA Packaging Scheme into Polyplex Micelles for Enhanced Gene Expression.
abstract: A critical role of polyethylene glycol (PEG) crowding in the packaging of plasmid DNA (pDNA) into polyplex micelles (PMs) was investigated using a series of PEG-b-poly(l-lysine) (PEG-PLys) block copolymers with varying molecular weights of both PEG and PLys segments. Rod-shaped PMs preferentially formed when the tethered PEG chains covering pDNA in a precondensed state were dense enough to overlap one another (reduced tethering density (RTD) > 1), whereas globular PMs were obtained when they were not overlapped (RTD < 1). These results submitted a scheme that steric repulsive effect of PEG regulated packaging pathways of pDNA either through folding into rod-shape or collapsing into globular depending on whether the PEG chains are overlapped or not. The rod-shaped PMs gave significantly higher gene expression efficacies in a cell-free system compared to the globular PMs, demonstrating the practical relevance of regulating packaging structure of pDNA for developing efficient gene delivery systems.
authors.forename: Kaori M
authors.identifier: 0000-0002-7067-4591
authors.initials: KM
authors.lastname: Takeda
authors.affiliation: Japan Science and Technology Agency, PRESTO , 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.|Innovation Center of NanoMedicine, Institute of Industrial Promotion - KAWASAKI , 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Osada
authors.affiliation: Innovation Center of NanoMedicine, Institute of Industrial Promotion - KAWASAKI , 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Theofilus A
authors.initials: TA
authors.lastname: Tockary
authors.affiliation: Innovation Center of NanoMedicine, Institute of Industrial Promotion - KAWASAKI , 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Anjaneyulu
authors.initials: A
authors.lastname: Dirisala
authors.forename: Qixian
authors.identifier: 0000-0002-3091-671X
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Innovation Center of NanoMedicine, Institute of Industrial Promotion - KAWASAKI , 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D002474:Cell-Free System; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D008823:Micelles; D010957:Plasmids / Q000737:chemistry* / Q000235:genetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D014162:Transfection
chemical_list: D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; D004247:DNA