RNA interference to tumor cells
Source: “Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles”
Mark E. Davis et al.
Nature 464: 1067-1070
Results: Researchers at Caltech used specialized nanoparticles to deliver a type of gene-silencing RNA to cancer cells in human subjects. Biopsies from three melanoma patients who had been given the therapy showed that the particles entered cancer cells but not healthy cells, and that the RNA successfully blocked the action of a cancer-related molecule that was its target.
Why it matters: Certain RNA molecules can cut messenger RNA and prevent it from producing proteins, a phenomenon known as RNA interference. But it has been difficult to deliver RNA-based therapies into the right cells. RNA injected into the bloodstream is typically filtered out by the kidneys before reaching its target, so the therapy has been limited to areas where the molecules can be delivered directly, such as the eyes or lungs. The new trial is the first to show that RNA can be ferried through the bloodstream in nanoparticles that protect the molecules and deliver them to cancer cells.
Methods: Researchers started with an RNA molecule designed to silence a gene used for DNA synthesis and repair. They enclosed the RNA in nanoparticles made of a sugar-based polymer, another polymer that binds weakly to water to enhance the particles’ stability, and a protein that is displayed on the particles’ exterior and binds with receptors on cancer cells, signaling the cells to absorb them. Once inside those cells, the nanoparticles release the RNA molecules to attack their targets.
Next steps: Researchers are studying patients with other tumors in an early-stage trial. They won’t be able to assess how effective the treatment is at shrinking tumors until testing it in more patients.