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 language | English |
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Pages (from-to) | 2743-2749 |
Number of pages | 7 |
Journal | Molecular Pharmaceutics |
Volume | 9 |
Issue number | 9 |
DOIs | |
Publication status | Published - 4 Sep 2012 |
Externally published | Yes |
Keywords
- DNA dynamics
- PAMAM dendrimer dynamics
- polyplex DNA release
- polyplex NMR spectroscopy
- polyplexes