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Lab tool may spawn new antiviral drugs

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9:57pm, August 5, 2002
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A gene-silencing strategy that's increasingly popular in the laboratory may wend its way into the medicine cabinet. Several research groups have reported successfully using the technique, known as RNA interference (RNAi), against viruses, including HIV, hepatitis C virus, and poliovirus.

RNAi is based on the discovery that adding short, double-stranded RNA molecules to a cell can turn off the gene that the RNA matches. When a gene makes the protein encoded in its DNA, it first generates a single-stranded form of RNA called messenger RNA. In RNAi, the added RNA interferes with this messenger RNA, interrupting the production of the corresponding protein.

First demonstrated in worms and then in flies, RNAi was recently shown to work in mammalian cells (SN: 1/15/00, p. 36: For geneticists, interference becomes an asset). Biologists are enthusiastic about the technique because it provides them with a simple way to disrupt specific genes. If they know a gene's DNA sequence, they can easily create the double-stranded RNA needed to silence the gene.

In a flurry of recent articles, research groups have now shown that RNAi can thwart the activity of viral genes in infected cells. In the July Nature Medicine, for example, a team headed by Phillip A. Sharp of the Massachusetts Institute of Technology reports inhibiting AIDS virus replication by targeting several of the virus' genes with RNAi. The group also used RNAi to reduce the production of CD4, one of the cell-surface proteins that HIV latches onto when it infects cells. HIV had difficulty infecting cells treated this way.

Another research team, led by Jean-Marc Jacque of the University of Massachusetts Medical School in Worcester, reports similarly encouraging tests of RNAi against HIV in an upcoming Nature. Also, within the past few weeks, two other groups of scientists have published accounts in Nature of turning RNAi against the genes of poliovirus and the virus that causes hepatitis C.

All the recent RNAi work used cells growing in laboratory dishes. Researchers caution that it's proven difficult in the past to develop RNA-based therapies that actually work in people.

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