Special delivery
Carl Novina, MD, PhD, uses gel electrophoresis, or modified Northern blotting, to verify that RNAi tools called short hairpin RNAs are active in a cell.
As successful as it has been, RNAi isn't problem-free. One challenge is to extend the period over which the gene silencing remains effective. Another is to efficiently deliver the RNAi molecules into different types of cells. Working with Hahn and several other scientists, Dana-Farber's Carl Novina, MD, PhD, used harmless viruses called lentiviruses to transport the RNA-interceptors into cells. "The advantage is that lentiviruses infect not just dividing cells, as many others do, but non-dividing cells where we want to use RNAi to find a gene's function," says Novina.
In addition, a gene silenced by an RNAi-carrying lentivirus stays silenced — a contrast to some other delivery techniques whose effects are transient. "It is now possible to use a lentivirus to infect an embryonic stem cell and generate a mouse in which the short hairpin RNA is expressed continuously," Novina says. "With the advent of specialized lentiviruses, it is possible to turn RNAi on and off at specific times to discover when genes function," he adds.
Not too many years ago, says Hahn, genetic scientists were like the great explorers of the 16th century, sailing off to discover islands and continents. But just as these mariners eventually put themselves out of business as the world map got filled in, "We don't discover many new genes anymore," says Hahn. "Instead, we want to know which genes are broken in cancer, and what their function is. When we accomplish that, we can more easily envision ways to halt or cure the disease."
