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Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer

Gene Therapy volume 15, pages 18–29 (2008)Cite this article

Abstract

A novel class of cationic hyperbranched polymers, containing branched oligoethylenimine (OEI 800 Da) as core, diacrylate esters as linkers and oligoamines as surface modification, was synthesized and evaluated regarding their structure–activity relationship as gene carriers. We show that pseudodendritic core characteristics as well as different surface modifications on the core influence DNA-binding ability, cytotoxicity and transfection efficiency. As most promising gene carrier, the pseudodendrimer HD O, that is, the OEI 800 Da core modified with hexane-1,6-diol diacrylate and surface-modified with OEI 800 Da, was identified. HD O exhibits efficient DNA-condensing ability to nanosized polyplexes (100–200 nm), low cytotoxicity, a degradation half-life of 3 days at 37 °C at physiological pH and in vitro reporter gene-expression levels similar to high molecular weight linear and branched polyethylenimines (PEIs) (LPEI and BPEI). In vivo studies in mice reveal that HD O/DNA polyplexes upon i.v. tail-vein injection have the potential for transfection of tumor tissue at levels comparable to that obtained with LPEI. Importantly, HD O was better tolerated than LPEI, while transgene expression was more tumor-specific and much lower in all other investigated organs, especially in the lung (15 000-fold lower compared with LPEI).

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Acknowledgements

We gratefully thank Dr Lerche for 1H NMR spectroscopic measurements, Michael Günther for help with flow cytometry, Gelja Maiwald and Markus Kovac for support in animal experiments and Olga Brück for skillful assistance in preparing the manuscript. This work was supported by EC funded project GIANT, DFG SFB486 and SPP1230 and the excellence cluster Nanosystems Initiative Munich (NIM).

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  1. Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology–Biotechnology, Ludwig-Maximilians University, Munich, Germany

    V Russ, H Elfberg, C Thoma, J Kloeckner, M Ogris & E Wagner

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Correspondence to E Wagner.

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Supplementary information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Russ, V., Elfberg, H., Thoma, C. et al. Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer. Gene Ther 15, 18–29 (2008). https://doi.org/10.1038/sj.gt.3303046

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