Tissue Factor siRNA for treatment of melanoma metastasis

The project described herein covers the research and initial preclinical part of the project of developing a drug based on small interfering RNAs (siRNA) targeting Tissue Factor, a molecule known to be involved in the processes of blood clotting, metastas is and angiogenesis. The project has emphasis on the first steps of risk reduction, to enable a decision for bringing one or more compounds into clinical trials. Tissue Factor (TF), the target for the drug developed under this application, has been implic ated in various processes promoting cancer development and spreading, including angiogenesis and metastasis. Early pre-clinical data demonstrated that systemic delivery of complexed siRNA molecules targeting TF can inhibit metastasis in various experiment al animal models, validating TF-specific siRNA as a viable therapeutic avenue. siRNAsense has systematically evaluated available delivery systems for use in humans, and have chosen three different systems for testing in vivo in rodents. The TF-specific si RNA in the optimal biologically relevant delivery system will go trough comprehensive functional and pharmaceutical analysis and detailed testing in rodents. This project will be follewed by analysis and detailed testing in non-human primates, and a prepa ration of an IND application, and planning for clinical phase I.