Polyamidoamine dendrimer-like polymer particles have been found to mediate high levels of exogenous gene transfer in vitro. Interestingly, the intact dendrimers show significantly reduced transfection activity levels; it is the partly degraded dendrimer-like polymers that exhibit the high activity levels that rival the best cationic lipid delivery systems. We think this mild degradation augments the flexibility of the polymer. We are using the Computer Graphics Laboratory facilities to help visualize: first, the general conformational structures adopted by these polymers under various physiological conditions that they encounter; and second, the conformation of the DNA/dendrimer complex, at least at a local level. Finally, we hope that comparative analysis of the structures of the intact and partially degraded dendrimers will provide insight into the mechanisms that occur at the molecular and cellular levels to induce transfection.
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