Off-Target Effects Plague Drosophila RNAi

Two new studies suggest a major body of research may need to be reevaluated

Jeffrey M. Perkel
Sep 10, 2006
Thousands of hits from dozens of genome-wide RNA interference screens in Drosophila cell cultures may need to be reevaluated, according to a pair of studies published this week in Nature and Nature Methods. The two reports demonstrate for the first time that so-called "off-target effects" (OTEs) can occur in experiments using long double-stranded RNA triggers for RNAi. "This [Nature] paper is potentially relevant to folks using libraries that can produce multiple triggers, multiple small RNAs," Greg Hannon of Cold Spring Harbor Laboratory said. Hannon, who did not participate in either study, noted that a 500-bp dsRNA could yield two dozen or more short RNAs, some of which could conceivably go astray. "So you run a primary screen, and you'll get a mix of on- and off-target effects. However, the ways that these screens are presently done solves this problem through the use of multiple independent dsRNA triggers." Off-target effects...