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Polymers 2017, 9(5), 161; doi:10.3390/polym9050161

Highly Branched poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) for High Performance Gene Transfection

1
Charles Institute of Dermatology, University College Dublin, Dublin 4, Ireland
2
Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
3
School of Food Science and Environmental Health, College of Sciences and Health, Dublin Institute of Technology, Dublin 2, Ireland
*
Authors to whom correspondence should be addressed.
Academic Editor: Ravin Narain
Received: 15 March 2017 / Revised: 26 April 2017 / Accepted: 27 April 2017 / Published: 1 May 2017
(This article belongs to the Special Issue Polymers and Nanogels for Gene Therapy)
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Abstract

The top-performing linear poly(β-amino ester) (LPAE), poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (C32), has demonstrated gene transfection efficiency comparable to viral-mediated gene delivery. Herein, we report the synthesis of a series of highly branched poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (HC32) and explore how the branching structure influences the performance of C32 in gene transfection. HC32 were synthesized by an “A2 + B3 + C2” Michal addition strategy. Gaussia luciferase (Gluciferase) and green fluorescent protein (GFP) coding plasmid DNA were used as reporter genes and the gene transfection efficiency was evaluated in human cervical cancer cell line (HeLa) and human recessive dystrophic epidermolysis bullosa keratinocyte (RDEBK) cells. We found that the optimal branching structure led to a much higher gene transfection efficiency in comparison to its linear counterpart and commercial reagents, while preserving high cell viability in both cell types. The branching strategy affected DNA binding, proton buffering capacity and degradation of polymers as well as size, zeta potential, stability, and DNA release rate of polyplexes significantly. Polymer degradation and DNA release rate played pivotal parts in achieving the high gene transfection efficiency of HC32-103 polymers, providing new insights for the development of poly(β-amino ester)s-based gene delivery vectors. View Full-Text
Keywords: non-viral vectors; gene therapy; transfection efficiency; cytotoxicity; nanoparticles; poly(β-amino ester)s non-viral vectors; gene therapy; transfection efficiency; cytotoxicity; nanoparticles; poly(β-amino ester)s
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zeng, M.; Zhou, D.; Ng, S.; Ahern, J.O.; Alshehri, F.; Gao, Y.; Pierucci, L.; Greiser, U.; Wang, W. Highly Branched poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) for High Performance Gene Transfection. Polymers 2017, 9, 161.

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