Abstract
Uncontrolled interactions of gene vectors and drug carriers in and with an in vivo environment pose serious limitations to their applicability. In order to reduce such interactions we have designed, synthesized and applied novel copolymers of poly(ethylene glycol) and reactive linkers which are derivatized with anionic peptides after copolymerization. The anionic copolymer derivatives are used to coat positively charged nonviral gene vectors by electrostatic interactions. The copolymer coat confers to polyelectrolyte colloids of DNA and polycations steric stabilization in their minimal size and prevents salt- and serum albumin-induced aggregation. Furthermore, complement activation and the interaction with serum proteins are drastically reduced or abolished in contrast to unprotected DNA complexes. The designed vectors are compatible with the intracellular steps of gene delivery and can even enhance transfection efficiency as demonstrated with various adherent and nonadherent cell lines in culture. The synthetic concept is amenable to the principles of combinatorial chemistry and the copolymeric products may be applicable beyond gene delivery in targeted drug delivery.
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Acknowledgements
This work was supported by grants from the German Ministry of Science (BMBF 01GE96179), the Deutsche Forschungsgemeinschaft (SFB 456) and by Boehringer Ingelheim Austria. We warmly thank Karl Mechtler, IMP Vienna, for his help in peptide synthesis and mass spectroscopy and Ursula Putz for excellent technical assistance. We wish to thank Dr Anton Steger for his help in purifying bulk quantities of polymers.
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Finsinger, D., Remy, JS., Erbacher, P. et al. Protective copolymers for nonviral gene vectors: synthesis, vector characterization and application in gene delivery. Gene Ther 7, 1183–1192 (2000). https://doi.org/10.1038/sj.gt.3301227
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DOI: https://doi.org/10.1038/sj.gt.3301227
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