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Abstract: PAMAM dendrimers is a new class of highly branched spherical polymers and has a unique surface of positively charged primary amine groups. They can form complex with DNA by electrostatic interaction, and delivery gene into cells. In this work, the ability of G5 PAMAM dendrimers binding and transferring DNA to cells has been investigated, the effect of PAMAM dendrimers/DNA complex to cell viability was evaluated, and the tissue distribution and biocompatibility of PAMAM dendrimers/DNA complex was analyzed. It was found that G5 PAMAM dendrimers could bind DNA and transfer it to cultured cells efficiently with low cycotoxicity. The complex of PAMAM dendrimer/DNA could remain intact in a broad pH range, and also could prevent DNA from being degraded by restriction enzyme. Taken as marker genes, the EGFP-C2 gene could be delivered by PAMAM dendrimers to many organs after intravenous injection and had high expression in liver, kidney, lung and spleen. It also could be found that PAMAM dendrimers/DNA complex could selectively bind with some kinds of plasma proteins, which may be correlated with its transportation in vivo. The leukemia’s gene therapy with PAMAM dendrimers/p16 and LRRC4 genes is being carried on currently. In conclusion, PAMAM dendrimers, a high-efficiency, low-cytotoxicity gene vector, appears to have potential for fundamental research and genetic therapy in vitro and in vivo.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA