Intrinsic Dynamics of DNA–Polymer Complexes: A Mechanism for DNA Release
2012-09-04T00:00:00Z (GMT)
by
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 (
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