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Authors Zhou, D. ; Gao, Y. ; Aied, A. ; Cutlar, L. ; Igoucheva, O. ; Newland, B. ; Alexeev, A. ; Greiser, U. ; Wang, W.
Title Highly branched poly(beta-amino ester)s for skin gene therapy
Date 28.12.2016
Number 53714
Abstract Poly(ß-amino ester)s (PAEs) have emerged as a promising class of gene delivery vectors with performances that can even be compared to viruses. However, all of the transfection studies (over 2350 PAEs) have been limited to linear poly(ß-amino ester)s (LPAEs) despite increasing evidence that polymer structure significantly affects performance. Herein, we describe the development of highly branched poly(ß-amino ester)s (HPAEs) via a new A2 + B3 + C2 Michael addition approach demonstrating 2 to 126-fold higher in vitro transfection efficiencies of different cell types in comparison to their linear LPAE counterparts as well as greatly out-performing the leading transfection reagents SuperFect and the gold-standard polyethyleneimine (PEI) - especially on skin epidermal cells. More importantly, the ability to correct a skin genetic defect is demonstrated in vivo utilizing a recessive dystrophic epidermolysis bullosa (RDEB) knockout mouse model. Our results provide evidence that the A2 + B3 + C2 approach can be controlled and offers sufficient flexibility for the synthesis of HPAEs. The branched structures can significantly improve the transfection efficiency and safety of PAEs highlighting the great promise for the successful application of non-viral gene therapy in skin disease.
Publisher Journal of Controlled Release
Wikidata
Citation Journal of Controlled Release 244 (2016) 366-346
DOI https://doi.org/10.1016/j.jconrel.2016.06.014
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