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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 (

SUBMITTER: Prevette LE

PROVIDER: S-EPMC3436429 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Intrinsic dynamics of DNA-polymer complexes: a mechanism for DNA release.

Prevette Lisa E LE Nikolova Evgenia N EN Al-Hashimi Hashim M HM Banaszak Holl Mark M MM

Molecular pharmaceutics 20120820 9

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(ethylene ...[more]

PMID: 22823140

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