Intrinsic dynamics of DNA-polymer complexes: A mechanism for DNA release

Lisa E. Prevette, Evgenia N. Nikolova, Hashim M. Al-Hashimi, Mark M. Banaszak Holl

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2743-2749
Number of pages7
JournalMolecular Pharmaceutics
Volume9
Issue number9
DOIs
Publication statusPublished - 4 Sep 2012
Externally publishedYes

Keywords

  • DNA dynamics
  • PAMAM dendrimer dynamics
  • polyplex DNA release
  • polyplex NMR spectroscopy
  • polyplexes

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