Silence is golden
Harnessing the power of RNAi gene-silencing technology to improve cancer treatment
By Richard Saltus
Carl Novina, MD, PhD, is studying the gene-silencing technique called RNA interference.
Every so often, innovations come along — like cell phones or the Internet — that are literally life-changing, leaving us wondering how we ever got along without them.
Scientists are feeling this way about a recently developed process for inactivating, or "silencing," any particular gene, be it in a single cell, a mouse, or even a human. They are thrilled to have the technique, known as "RNA interference," because it has dramatically speeded up experiments aimed at discovering genes' roles by turning them off — in cancer cells, for example — to see what effect it has.
By analogy, it's like flipping switches in a fuse box to determine which of them controls specific circuits, lights, and appliances of a house.
RNAi, as it's abbreviated, is an enormous boon to studies like these, and its discovery captured this year's Nobel Prize in medicine. Until now, it has been a long and laborious process to discover genes' functions by disabling them, usually by breeding "knockout mice" lacking a certain gene. RNAi can do much the same thing far more rapidly, opening new experimental possibilities for accelerated, large-scale gene function studies. Unlike knockout mice, RNAi technology doesn't totally block genes' ability to make proteins — known as gene "expression" — but can reduce it to a very low level. Nevertheless, researchers use the terms gene "silencing" and "inactivation" when referring to RNAi.
"The specificity and flexibility of RNAi guarantee that it will become standard and essential component of everyone' scientific toolbox."
—Barrett Rollins, MD, PhD
"In simple terms, RNAi lets you inactivate any gene you're interested in at any time. This has rapidly become an essential and powerful tool," says Barrett Rollins, MD, PhD, Dana-Farber's chief scientific officer. "The specificity and flexibility of RNAi guarantee that it will become a standard and essential component of everyone's scientific toolbox."
In biology labs everywhere, RNAi tools are changing the way science is done. With a focus on cancer, scientists at Dana-Farber, along with colleagues at the Broad Institute of the Massachusetts Institute of Technology and Harvard University, have deployed RNAi technology in a hunt for genes they call cancer's "Achilles' heels" – genes behaving abnormally that tumors depend on to grow, survive, and progress. Using a specific type of RNAi tool called "short hairpin RNAs," or shRNAs, scientists can sequentially turn off genes in thousands of different cancer cells to find out which genes, when silenced, cause the cells to weaken or die. Identifying such genes would be the starting point for developing new drugs to target them.
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