Yesterday, together with his colleagues, Mark Davis from the California Institute of Technology in Pasadena published their findings of a study in Nature magazine on the method that they developed to deliver short sequences of RNA to human melanomas, interrupting the replication process of the cancerous cells.
The technique of using these short RNA sequences to turn off, or silence, specific genes was coined RNA interference (RNAi) by Craig C. Mello and Andrew Fire, 2 American biologists who were awarded the Nobel Prize in Physiology or Medicine in 2006 for their research into the phenomenon, which they first reported in a paper in Nature in 1998. However, since then there has not been much success in getting this process to the clinic, due in part with difficulties in the delivery of the sequences to the intended target. The method developed by the team from Caltech uses nanoparticles to help solve this problem. Using two polymers plus a protein that binds to both receptors that are on the surface of cancer cells and siRNA (small-interfering RNA), the researchers are able to inhibit the expression of a key gene, RRM2, preventing it from being translated into protein, and thus halting it from multiplying.
The particles themselves used in this process are about 70 nanometers in diameter. They are introduced into a patients blood stream, which they travel through until they encounter the tumors. They then binds to the cells of the tumor, and get absorbed. The nanoparticles then fall apart, unbinding the polymers from the siRNA, which then sticks to the cell’s messenger RNA (mRNA), halting the translation process. The polymers then pass out of the body through the urine.
While further testing is needed to make sure that therapies using this method are safe, Davis has hopes that the treatments will have no major side effects. “My hope is to make tumours melt away while maintaining a high quality of life for the patients,” he says. “We’re moving another step closer to being able to do that now.”
Further reading Cancer genes silenced in humans.