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Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain

Newland, B. ORCID:, Aied, A., Pinoncely, A. V., Zheng, Y., Zhao, T., Zhang, H., Niemeier, R., Dowd, E., Pandit, A. and Wang, W. 2014. Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain. Nanoscale 6 (13) , pp. 7526-7533. 10.1039/C3NR06737H

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The purpose of this study was to develop a platform transfection technology, for applications in the brain, which could transfect astrocytes without requiring cell specific functionalization and without the common cause of toxicity through high charge density. Here we show that a simple and scalable preparation technique can be used to produce a “knot” structured cationic polymer, where single growing chains can crosslink together via disulphide intramolecular crosslinks (internal cyclizations). This well-defined knot structure can thus “untie” under reducing conditions, showing a more favorable transfection profile for astrocytes compared to 25 kDa-PEI (48-fold), SuperFect® (39-fold) and Lipofectamine®2000 (18-fold) whilst maintaining neural cell viability at over 80% after four days of culture. The high transfection/lack of toxicity of this knot structured polymer in vitro, combined with its ability to mediate luciferase transgene expression in the adult rat brain, demonstrates its use as a platform transfection technology which should be investigated further for neurodegenerative disease therapies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Royal Society of Chemistry
ISSN: 2040-3364
Date of First Compliant Deposit: 31 October 2017
Date of Acceptance: 15 April 2014
Last Modified: 06 Nov 2023 23:54

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