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Design and Synthesis of a Polyguanidium Vector with Enhanced DNA Binding Ability for Effective Gene Delivery at Low N/P Ratio

Abstract

Synthetic cationic polymers are commonly used vectors for non-viral gene delivery. However, the transfection efficiencies of such vectors are inevitably linked to their cytotoxicity, because positive charge density of the polymers is the decisive factor of both. High charge density is necessary for the gene condensation and intracellular internalization, while it also leads to undesired toxicity mainly due to membrane disruption. To address this problem, in this work we introduced a new DNA binding driving force into the polymeric vector, using a guanidium-on-backbone polymer to facilitate efficient gene condensing. In addition to electrostatic interactions, polyguanidium provided extra affinity toward DNA by serving as a multivalent minor groove binder. It was shown that this polymer could tightly condense gene at relatively low charge ratios using N/P ratio as low as 2.5:1, and give gene transfection efficiency comparable to commercial available reagent, 25 kDa polyethyleneimine. Such polymer also exhibited relatively low toxicity, benefited from its lower positive charge density.

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Publication details

The article was received on 02 Oct 2019, accepted on 03 Dec 2019 and first published on 04 Dec 2019


Article type: Communication
DOI: 10.1039/C9PY01481K
Polym. Chem., 2019, Accepted Manuscript

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    Design and Synthesis of a Polyguanidium Vector with Enhanced DNA Binding Ability for Effective Gene Delivery at Low N/P Ratio

    Z. Chen, W. Huang, N. Zheng and Y. Bai, Polym. Chem., 2019, Accepted Manuscript , DOI: 10.1039/C9PY01481K

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