To test this idea out, they injected their nanoparticles into mice that had been engineered to suffer from Ewing’s sarcoma, a rare childhood cancer.
They chose this disease because it is caused by a novel gene not found in healthy individuals, and thus provides a clear and unambiguous target for the therapeutic RNA. The novel gene is created when two chromosomes, numbers 11 and 22, each break in two at particular weak spots, and part of chromosome 11 joins with part of chromosome 22. As bad luck would have it, the DNA at the junction forms a sequence that the cell’s gene-reading machinery recognises as a gene, and this gene spurs uncontrolled cell growth (in other words, cancer) in certain bone and muscle cells.
Mice injected with human Ewing’s sarcoma cells develop secondary cancers similar to those seen in human patients. However, when the researchers injected their nanoparticles into the bloodstreams of animals with Ewing’s tumours, the growth of those tumours slowed. Even better, if they injected the animals with nanoparticles shortly after injecting the cancer cells, they stopped the formation of secondary cancers in the first place.
Other scientists have shown that they can use RNAi to slow tumour growth in mice, but they have had to inject their RNA directly into the tumour, which is tricky. Dr Hu, Dr Triche and Dr Davis are the first to demonstrate that they can inject it into an animal’s bloodstream and then let it find its own way to the target.
The three researchers are now working to perfect the system, so that it can be tested in people, and they are also making sure that it works in cancers other than Ewing’s sarcoma. If they can do both of these things, they may have come up with the much-sought mechanism for propelling RNAi into the big time.