The ability to turn genes both on and off may have major implications for the treatment of diseases. For example, the development of cancer may be partially due to mutations in genes that control cell growth. The body contains genes that are natural tumor suppressors. Mutations that silence these genes may result in uncontrolled cancer growth. Janowski and Corey believe that finding a way to turn these genes back on may stem the growth of tumor cells.
However, they say it’s not clear exactly how RNA’s genetic “on” switch works. In their experiments, the researchers injected RNA directly into cancer cells, where it interacted with specific genes to turn them on. Janowski says this may be a more direct method compared with conventional RNAi techniques, in which scientists inject RNA strands outside a cell to block messenger RNA–an intermediary molecule that delivers genetic information out of a cell to surrounding proteins that act out a gene’s instructions.
“It’s easier to turn something off by acting like a roadblock so the transcriptional machinery can’t get past it,” says Janowski. “But to activate it is harder to do.”
Gordon Carmichael, professor of genetics and developmental biology at the University of Connecticut Health Center, studies RNA’s role in regulating disease. While Carmichael did not attend the conference, he is familiar with the team’s work and says the research is interesting, although puzzling. “The question arises as to whether the observed effects are general and, if so, how general?” he says. “There appear to be few genes that can be regulated this way.”
In future studies, Janowski and Corey plan to explore the exact mechanism for RNA’s genetic activating potential. They will also explore RNA’s effect in turning on a variety of genes, including tumor suppressor genes, and they hope eventually to experiment on animal models. However, Janowski acknowledges that the team’s work and its conclusions are preliminary.
Phillip Sharp, MIT professor and Nobel Prize-winning cancer researcher, advises a wait-and-see approach. Speaking from the RNAi conference in Colorado, Sharp says it may be a while before RNA’s genetic “on” switch is as scientifically confirmed as its “off” switch. “There will have to be a lot of additional work before one can judge the importance of this finding,” he says.
The University of Texas team, meanwhile, is optimistic. “Anything new will be a test of time,” says Janowski. “People are pretty open to new ideas, but because this has been so entrenched, it will take people a while to get a handle on this.”