San Francisco Chronicle - Monday, June 3, 2002
Sabin Russell, Chronicle Medical Writer

The process employs tiny pieces of RNA -- the coded molecules that contain blueprints for many viruses -- to smother the production of new viruses inside infected cells.

Known as "RNA interference" or "gene silencing," this ancient molecular weapon was discovered in plant cells only in 1998, and it has since prompted a flurry of research that found evidence of it in primitive worms, fruit flies and mammalian cells as well.

"Over the past year, people have been designing RNAs and silencing all sorts of genes. It's become a growth industry," said Dr. Phillip Sharp, a Nobel Prize-winning molecular biologist at the Massachusetts Institute of Technology.

Dr. Jay Levy, a UC San Francisco virologist who is also experimenting with interfering RNAs, said the newly discovered phenomenon is unlocking secrets that go beyond controlling viruses. "This thing is big," he said.

Silencing genes is the flip side of gene expression, the activation of a gene's instructions to make a certain protein. Gene silencing is the process of turning off genes and shutting down that production.

For a complex organism to develop from a single cell, genes need to switch on and off all the time. RNA interference appears to be one such "off switch."

Sharp and colleagues at MIT, in an online edition of the journal Nature Medicine being released today, describe test-tube experiments in which they used the interfering bits of RNA to slow the replication of HIV, the virus that causes AIDS. The article will be published in the July issue of the journal.

Dr. John Rossi and a team of researchers at the Beckman Research Institute at the City of Hope in Duarte (Los Angeles County) reported similar success in suppressing HIV with interfering RNA in last month's issue of the journal Nature Biotechnology.

Both teams of researchers used extremely short sequences of "double- stranded" RNA. It is a rarer form of the genetic material that winds itself into a helix similar to its more complex and better-known cousin, DNA. At MIT, two different approaches were tried against HIV: one to block the virus' entry into blood cells through a doorway known as CD4, the other interfering with the machinery used by the virus to make copies of itself.

Both approaches worked, but Sharp noted the effect was "neither complete nor permanent." After about a week, viral replication sped up again, but it could be slowed down by reintroducing the RNA.

Sharp said the experiment proved that RNA interference was a workable approach. It was, the authors wrote, "a proof-of-principle" the technology could be used to suppress many steps of the viral life cycle.

Sharp cautioned that these early experiments are a long way from producing even an experimental drug that could test the concept in humans. But he acknowledged that biologists are excited about the approach. "This is a whole new field," he said.

E-mail Sabin Russell at srussell@sfchronicle.com.

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