Can interfering with RNA shut down the macular degeneration process?
Imagine that age-related macular degeneration had an off switch. In fact, researchers may have found one for the most severe stage of age-related macular degeneration, by shutting down the genes that control vascular endothelial growth factor (VEGF). This molecule plays an important role in the abnormality known as wet (neovascular) age-related macular degeneration, in which new blood vessels grow under the retina.
Several biotechnology firms have succeeded in switching off blood-vessel growth using a technique that scientists call RNA interference, or RNAi. The common term for the process is more descriptive: gene silencing. The scientists who worked out the details of this process of RNA interference won the Nobel Prize for Physiology and Medicine in 2006.
RNA is a chemical responsible for translating the genetic code within DNA into proteins, the molecules that are the basis for cell structure and molecular signaling between cells. Most of the time, RNA exists in a single strand. But when RNA appears in a double strand (one RNA strand matching the other as a chemical mirror image), cells destroy it and any other RNA like it. This process may have arisen to guard against viruses, which sometimes create double-stranded RNA.
Eventually, the process of RNA interference may prove useful against diseases such as cancer, AIDS, and hepatitis. But age-related macular degeneration has proven an easier target, partly because researchers already know some genes to block, such as the ones that control VEGF production. Also, although it is a major challenge to deliver siRNA to the right cellular target in diseases that affect the entire body, in the case of age-related macular degeneration this is straightforward. The siRNA can be introduced directly into the eye, by injecting it into the vitreous cavity (the jelly-like substance in the center of the eye).
Much remains to be determined, such as how long RNAi will suppress the VEGF gene, how much is required and how often, and whether this treatment is safe and effective against wet age-related macular degeneration. Several new clinical studies designed to resolve these questions are well underway.
