The RNAi Revolution

author: Phillip A. Sharp, Department of Biology, Massachusetts Institute of Technology, MIT
published: March 5, 2011,   recorded: June 2006,   views: 4093
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When a Nobel Prize-winning pioneer of molecular biology embraces a new area of research as revolutionary, attention must be paid. Phillip A. Sharp’s own discoveries involving gene expression opened up new territory in the search for the genetic causes of cancer and other diseases. He now has great hopes for similar breakthroughs with the process of gene silencing.

This latest advance in understanding gene regulation is quite recent. In 1998, Andrew Fire and Craig Mello discovered the process of RNA interference in the worm C. elegans. When they introduced short, double strands of synthesized RNA into a cell, the RNA silenced a gene in the cell and turned off a specific protein. (Fire and Mello were awarded the 2006 Nobel for this work.) Previously, scientists had viewed RNA as simply “the slave molecule between DNA and protein,” as Sharp puts it, or in spliced form, capable of generating a great number of diverse proteins. But revelation of the mechanism of interfering RNA has made the field “a lot more interesting,” says Sharp.

In just a few years, researchers have learned that small RNA “taps into a pathway that’s present in every cell,” says Sharp. “At minimum, one in four or one in five of our genes is controlled by small RNAs.” Researchers also suspect RNA pathways may occupy a central role in establishing controls in the “human germ line” to prevent redundant pieces of DNA from being expressed in a destructive way. This offers researchers more than a powerful, new investigative tool. Says Sharp, “This is MIT. If you’ve got something in the lab that’s new and you know people need it outside of the lab, you’re under an obligation to try to translate it into therapy.” One big question is whether small RNA can be used to treat cancers.

There’s evidence that small RNAs injected directly into the eyeball can potentially silence interconnecting genes responsible for cancers in the back of the eye. The same technique might also work for cancers in the brain and lung, says Sharp. One challenge involves getting the highly water soluble RNA across the cell membrane. Nanoparticle packaging may help prevent the RNAs from being absorbed before they’re delivered to the target area. Sharp also mentions experiments that suggest misregulation of small RNAs can cause cancer. “We as a field are now struggling with the issue of just what role short RNAs play in general in control of our genes and our normal physiological processes. It’s getting really interesting.”

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