This group has designed a mammalian expression vector that directs the synthesis of siRNA-like transcripts (pSUPER, suppression of endogenous RNA). We have successfully used this vector to stably suppress expression of more than one hundred different genes with no associated toxicity. As part of our contribution to the EuroFOG program, we will use this vector system to generate a large collection of some 6,000 siRNA vectors that each targets a single gene, specifically focussed on ESTs and poorly characterised genes. This collection of siRNA vectors will allow us for the first time to perform large-scale screens for loss-of-function phenotypes. The vector set will be shared with the other members of the TRANSFOG consortium to carry out genetic screens in pathways of their interest. NKI will be coordinator of WP3, aimed at generating the siRNA collection.

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