An additional mechanism that may lead to nonspecific effects in vivo relies on the interferon system [30] [31] [32] [33] which is induced when double-stranded RNA molecules enter a cell activating a multi-component signalling complex. This effect is particularly true for long dsRNA molecules and essentially prevents them from being used as inducers of RNA interference in mammalian systems. The development of synthetic siRNAs [10, 12, 33, 34] largely circumvents this problem since they seem to be too small. However, some synthetic siR-NAs do induce components of the interferon system which seems to be dependent on their sequence [31, 32, 35] as well as, in the case of in vitro transcribed siRNAs, on the 5 initiating triphosphate [36] . Thus, strategies to avoid as far as possible the unwanted interferon response upon application of siRNAs in vivo will include a design of siRNAs without known interferon-stimulating sequences, the use of the lowest possible siRNA dose to still achieve the desired effect and optimized siRNA delivery methods.