A novel hybrid dendrimer (TRANSGEDEN) that combines a conjugated rigid polyphenylenevinylene (PPV) core with flexible polyamidoamine (PAMAM) branches at the surface was synthesized and characterized. The potential of this material as a nonviral gene delivery system was also examined, and it was observed that dendriplexes formed by TRANSGEDEN and small interfering ribonucleic acids (siRNAs) can be incorporated into >90% of neuronal cells without any toxicity up to a dendrimer concentration of 3 mu M. TRANSGEDEN was used to deliver a specific siRNA to rat cerebellar granular neurons (CGNs) to knock down the cofilin-1 protein. Cofilin-1 removal partially protects CGNs from N-methyl D-aspartate (NMDA)-mediated neuronal death.