mp3002864_si_001.pdf (241.62 kB)
Intrinsic Dynamics of DNA–Polymer Complexes: A Mechanism for DNA Release
journal contribution
posted on 2012-09-04, 00:00 authored by Lisa E. Prevette, Evgenia N. Nikolova, Hashim M. Al-Hashimi, Mark M. Banaszak HollThe 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 (