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Polyelectrolyte nanoparticles mediate vascular gene delivery

 
: Zaitsev, S.; Cartier, R.; Vyborov, O.; Sukhorukov, G.; Paulke, B.-R.; Haberland, A.; Parfyonova, Y.; Tkachuk, V.; Böttger, M.

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Pharmaceutical research 21 (2004), Nr.9, S.1656-1661
ISSN: 0724-8741
ISSN: 0739-0742
Englisch
Zeitschriftenaufsatz
Fraunhofer IAP ()

Abstract
Purpose. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues.
Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core.
Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant.
Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.

: http://publica.fraunhofer.de/dokumente/N-29573.html