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Polysaccharide-oligoamine Based Conjugates For Gene Delivery.

T. Azzam, H. Eliyahu, L. Shapira, M. Linial, Y. Barenholz, A. Domb
Published 2002 · Chemistry, Medicine

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This work describes a versatile and universal polycation system based on oligoamines grafted on natural polysaccharides that is capable of complexing various plasmids and administering them into various cells in high yield to produce a desired protein. These polycations are expected to better meet the requirements for effective complexation and delivery of plasmid or an antisense and to biodegrade into nontoxic components at a controlled rate. The developed biodegradable polycations are based on spermine, a natural tetramine, conjugated to dextran or arabinogalactan. These polycations were prepared by reductive amination of oxidized polysaccharides with the desired oligoamines. The Schiff base conjugates thus obtained were reduced to the stable amine conjugates by sodium borohydride. Over 300 different polycations were prepared starting from various polysaccharides and oligoamines, mainly oligoamines of two to four amino groups. Although most of these conjugates formed stable complexes with various plasmids as determined by turbidity experiments, only a few polycations were found to be active in transfecting cells. This work indicates that the structure of the polycation plays a significant role in the transfection activity of polycations.
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