In many animals, siRNAs can only function within the cell in which the siRNA is introduced. In contrast, the worm Caenorhabditis elegans can be fed with bacteria that synthesize double-stranded RNAs, and the RNAi spreads throughout the animal. A genetic screen to identify genes involved in systemic RNAi led to the discovery of Sid-1, a transmembrane protein expressed in most tissues in the adult worm. Loss-of-function mutations in the gene encoding Sid-1 restrict the RNAi activity to the cells surrounding the digestive tract after siRNA feeding. Ectopic expression of Sid-1 in Drosophila melanogaster cells that normally lack systemic RNAi and are unable to take up siRNAs from the medium, enables these cells to passively take up siRNA . These findings suggest that …