The receptor ligand, VEGF, is a mitogenic and angiogenic growth factor stimulating tumor growth and angiogenesis in several tumors including prostate carcinoma. Thus, it may represent attractive target molecule for RNAi-based genetargeting strategies also bearing in mind the double antitumoral effect due to reduction of tumor cell proliferation as well as tumor angiogenesis. The subcutaneous or intraperitoneal injection of VEGF-specific siRNAs complexed with a novel PEI obtained through fractionation of a commercially available PEI (Werth et al, in press) resulted in the reduction of tumor growth due to decreased VEGF expression levels (Höbel and Aigner, unpublished results). The same was true for PEI/siRNA-mediated targeting of FGF-BP (Dai and Aigner, unpublished results), which has been established Figure 3 : Protection and in vivo delivery of siRNAs upon PEI complexation. In [70] (a) in vitro protection of siRNAs against nucleolytic degradation. [ 32 P] end-labeled siRNAs, complexed (upper panel) or not complexed (lower panel) with PEI, were subjected to treatment with 1 % fetal calf serum at 37 • C. At the time points indicated, the samples were analysed by agarose gel electrophoresis, blotting, and autoradiography. The bands represent full-length siRNA molecules indicating that PEI complexation leads to the efficient protection of siRNAs while noncomplexed siRNAs are rapidly degraded. (b,c) In vivo delivery of intact siRNAs upon PEI complexation. [ 32 P]-labeled siRNAs, complexed (+) or not complexed (−) with PEI, were injected IP into mice bearing subcutaneous SKOV-3 ovarian carcinoma cell tumor xenografts, and after 30 min (b) or 4 h (b) total RNA from various organ and tissue homogenates was prepared and subjected to agarose gel electrophoresis prior to blotting and autoradiography. The bands represent intact [ 32 P]-labeled siRNA molecules which for several hours are mainly found in tumor and muscle as well as in liver and, time-dependently, in kidney. Only little siRNA amounts are detected in the lung and traces in the brain.