RNA treatment kills mice

May 30, 2006

Using RNA interference to shut down harmful genes can have fatal flaw.

The research shows that mice can die when injected with high doses of a form of RNA. The RNA molecules, which were folded into structures called short hairpin RNAs (shRNAs), were able to overwhelm a cell's normal RNA-processing mechanisms, with fatal consequences.

Researchers say the work emphasizes the need to proceed carefully towards human trials of RNA interference, a scheme by which RNA is used to shut down harmful genes. Such trials are already underway for a condition known as macular degeneration and a childhood infection called respiratory syncytial virus. And a slew of new trials are planned to treat conditions such as HIV, hepatitis and even bird flu.

Safety concerns about RNA interference have been raised before. Scientists have already reported that some forms of the technique can shut down unintended genes, or trigger a cellular defence mechanism known as the interferon response2. That could lead to harmful side effects.

Source:
Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways.
Nature 441, 537-541 (25 May 2006)

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