Long-term use of RNA interference (RNAi) can be fatal in mice, scientists report in this week's Nature. However, some short hairpin RNAs (shRNAs) suppressed viral infections without killing the mice, suggesting that the technology may still be useful -- if used carefully. This shows RNAi therapies "can be very effective, but [scientists] will have to really test the sequences and doses [they] want in clinical trials," John Rossi of the Beckman Research Institute of the City of Hope in Duarte, Calif., who did not participate in this study, told The Scientist.Study author Mark Kay at Stanford University in California and his colleagues, led by postdoctoral researcher Dirk Grimm, began investigating the long-term effects of RNAi after a 2003 study of shRNAs against hepatitis B yielded some disappointing results. Although the initial findings were promising, "then we saw some dying two or three weeks later," Kay told...

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