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MIT helps make RNA interference "breakthrough of the year"

The Dec. 20 issue of Science magazine names RNA interference, or RNAi, the "breakthrough of the year" of 2002.

MIT and the Whitehead Institute for Biomedical Research have been involved from the start in this recently discovered method of turning off genes using short pieces of RNA.

"RNAi is the most important and exciting breakthrough of the last decade, perhaps multiple decades," said Phillip A. Sharp, professor and director of MIT's McGovern Institute for Brain Research and a Nobel laureate in biology.

RNA was long thought to be only DNA's messenger, an intermediary that delivered the genetic code for proteins. Researchers have now found that tiny double strands of RNA can shut down any given gene. RNA medicines could be developed to treat a host of disorders, from high cholesterol to cancer, as well as viral diseases such as AIDS.

Laboratory techniques using RNAi also can be used to uncover the functions of particular genes.

Andrew Fire, who graduated from MIT with a Ph.D. degree in 1983, was at the Carnegie Institute of Washington when he found that injecting complementary single strands of RNA into worms resulted in a potent silencing effect when the two strands combined. He and geneticist Craig Mello dubbed the phenomenon "RNA interference."

These researchers "have changed the future of biological science by providing insights into the ability of RNA to regulate gene expression," Sharp said.

At MIT, David P. Bartel, associate professor of biology and a member of Whitehead, studies RNA-mediated cellular processes, including RNAi and microRNAs, small RNA molecules that also seem to silence genes. Bartel has identified hundreds of genes that code for them in a wide range of organisms. It was Thomas Tuschl, formerly a postdoctoral associate under Bartel, who announced at a 2001 meeting of the RNA Society that RNA fragments quickly and efficiently turn off genes in human cells.

The laboratory of 2002 Nobel laureate H. Robert Horvitz, professor of biology and a Howard Hughes Medical Institute investigator, has initiated a genomics/robotics project to analyze the more than 100 microRNAs encoded by the C. elegans (roundworm) genome.

Luk Van Parijs, the Ivan R. Cottrell Career Development Assistant Professor in Immunology, looks at how cell growth and cell death signals control immune function and disease. His laboratory is testing whether autoimmune disease or cancer can be cured by specifically targeting immune cell survival molecules using RNA interference methods.

Phil Zamore, a biochemist at the University of Massachusetts Medical School in Worcester, and Sharp made several important contributions. Last June, Sharp showed that small interfering RNAs could stop HIV infection in cells grown in the lab. Sharp, former MIT biology professor Paul Schimmel, Zamore and others have co-founded Alnylam Pharmaceuticals in Cambridge to develop RNAi-based drugs.

"All of the science related to the discovery of RNAi and advances in the use of RNAi could have been done 15 years ago," Sharp said. "For social reasons, we did not ask the right questions. Students should take heart that there are still discoveries to be made."

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