Drosophila melanogaster has been a premier genetic model system for nearly 100 years, yet lacks a simple method to disrupt gene expression. Here, we show genomic cDNA fusions predicted to form double-stranded RNA (dsRNA) following splicing, effectively silencing expression of target genes in adult transgenic animals. We targeted three Drosophila genes: lush, white, and dGqα. In each case, target gene expression is dramatically reduced, and the white RNAi phenotype is indistinguishable from a deletion mutant. This technique efficiently targets genes expressed in neurons, a tissue refractory to RNAi in C. elegans. These results demonstrate a simple strategy to knock out gene function in specific cells in living adult Drosophila that can be applied to define the biological function of hundreds of orphan genes and open reading frames.
