A supplement providing a snapshot of the latest developments in chemical biology
Gene delivery with dendrimers
24 February 2006
Dendritic molecules developed as gene carriers show potential for cancer therapy say scientists in Switzerland.
Gene transfection, the delivery of genetic material into a cell is currently most efficient using viral vectors. In a step towards the development of synthetic vectors for use in drug delivery and gene therapy, François Diederich and colleagues at the Swiss federal institute of technology (ETH) Zürich have synthesised a family of dendritic molecules which have proved effective in vitro.
The success of viral gene carriers is partly attributed to their self assembly as this improves their passage through the cell membrane. With this in mind, the Swiss team incorporated lipophilic branches into the dendrimer. The lipophilic section was linked by an aromatic group to cationic branches involved in cellular uptake.
The structure of the two branched sections and the linking group were varied to determine their influence on the biological activity of the molecules in human cervical cancer cells. Their behaviour in Langmuir films was also analysed to investigate the potential correlation between the self assembly and the transfection efficiency of the dendrimers.
The nature of the lipophilic branches was found to be an important factor for the self assembly of the molecules into a film and for the transfection efficiency. The biological activity fell if the packing of the molecules was impaired. Varying the structure of the cationic branches had little effect on the biological activity; however, the aromatic core of the dendrimer also had some influence on the biological activity.
The challenge remains to create a dendrimer which is an efficient synthetic gene carrier in vivo and has low cytotoxicity, said Diederich.