Dendrimers can be used to switch off specific genes, say chemists in France and China.

Genes can be switched off (silenced) using short interfering RNA (siRNA), double strands of RNA which target a particular gene and prevent its expression. Now, Ling Peng of the Centre National de la Recherche Scientifique in Marseille, France, and colleagues have shown that dendrimers offer a way to deliver siRNA into cells for potent gene silencing.

PAMAM dendrimers, highly branched polymers with amine groups covering their surface, are known to bind DNA. Peng showed that these dendrimers also strongly bind siRNA. The resulting spherical nanoparticles are able to deliver the siRNA into cells effectively, while protecting it from RNA-digesting enzymes, Peng said.

The researchers used their system to silence a target gene in human lung cancer cells. The siRNA was released slowly by the dendrimer, giving long-term gene silencing that remained 50% effective even after 72 hours, said Peng. 

Being able to down-regulate, or silence, genes is an effective tool for investigating what a particular gene does, said Peng. The same procedure could be used in future medicines, switching off genes associated with disease, Peng said. 

The team now plans to fine-tune the dendrimer properties, to improve its siRNA delivery and reduce its toxicity. Andrew Marsh, a supramolecular chemist at the University of Warwick, UK, sees this as a key challenge for the team. 'The impact synthetic chemists can make to optimise the dendrimers for delivery to particular cell lines will be crucial in the further development of this exciting work,' said Marsh.

James Mitchell Crow