title: Intrinsic dynamics of DNA-polymer complexes: a mechanism for DNA release.
abstract: The transfer of genetic material into cells using nonviral vectors offers unique potential for therapeutics; however, the efficacy of delivery depends upon a poorly understood, multistep pathway, limiting the prospects for successful gene delivery. Mechanistic insight into DNA association and release has been hampered by a lack of atomic resolution structural and dynamic information for DNA-polymer complexes (polyplexes). Here, we report a dendrimer-based polyplex system containing poly(ethyleneglycol) (PEG) arms that is suitable for atomic-level characterization by solution NMR spectroscopy. NMR chemical shift, line width, and proton transverse relaxation rate measurements reveal that free and dendrimer-bound polyplex DNA exchange rapidly relative to the NMR time scale (<millisecond). The dendrimers retain a high degree of mobility in the polyplex, whereas the DNA shows restrained mobility, suggesting that the polyplex is a highly dynamic complex with a rapidly exchanging dendrimer atmosphere around a more rigid DNA framework.
authors: Department of Chemistry, University of Michigan, 911 North University Avenue, Ann Arbor, Michigan 48109, United States.
authors: Lisa E
authors: LE
authors: Prevette
authors: Evgenia N
authors: EN
authors: Nikolova
authors: Hashim M
authors: HM
authors: Al-Hashimi
authors: Mark M
authors: MM
authors: Banaszak Holl
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D050091:Dendrimers / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D011108:Polymers; D011092:Polyethylene Glycols; D004247:DNA