Rapid exchange between free and bound states in RNA-dendrimer polyplexes: Implications on the mechanism of delivery and release

Anisha Shakya, Casey A. Dougherty, Yi Xue, Hashim M. Al-Hashimi, Mark M. Banaszak Holl

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A combination of solution NMR, dynamic light scattering (DLS), and fluorescence quenching assays were employed to obtain insights into the dynamics and structural features of a polyplex system consisting of HIV-1 transactivation response element (TAR) and PEGylated generation 5 poly(amidoamine) dendrimer (G5-PEG). NMR chemical shift mapping and 13C spin relaxation based dynamics measurements depict the polyplex system as a highly dynamic assembly where the RNA, with its local structure and dynamics preserved, rapidly exchanges (<ms) between free and polyplex-bound forms, at least for the probed N/P ratios. Recovery of quenched fluorescence shows that RNA in the polyplex can be competitively exchanged over a wide range of amine to phosphate (N/P) charge ratios. The rapid exchange between free and bound forms may contribute to the mechanism by which RNA is released into the cell upon delivery while being protected by the polyplex environment from immediate degradation by nucleases.

Original languageEnglish
Pages (from-to)154-164
Number of pages11
JournalBiomacromolecules
Volume17
Issue number1
DOIs
Publication statusPublished - 11 Jan 2016
Externally publishedYes

Cite this

Shakya, Anisha ; Dougherty, Casey A. ; Xue, Yi ; Al-Hashimi, Hashim M. ; Banaszak Holl, Mark M. / Rapid exchange between free and bound states in RNA-dendrimer polyplexes : Implications on the mechanism of delivery and release. In: Biomacromolecules. 2016 ; Vol. 17, No. 1. pp. 154-164.
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Rapid exchange between free and bound states in RNA-dendrimer polyplexes : Implications on the mechanism of delivery and release. / Shakya, Anisha; Dougherty, Casey A.; Xue, Yi; Al-Hashimi, Hashim M.; Banaszak Holl, Mark M.

In: Biomacromolecules, Vol. 17, No. 1, 11.01.2016, p. 154-164.

Research output: Contribution to journalArticleResearchpeer-review

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