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GNBIO-Grunnleggende næringsrettet bioteknologi

RNA interference targeting Tissue Factor, a novel principle for cancer therapy.

Tildelt: kr 2,4 mill.

Prosjektleder:

Prosjektnummer:

165068

Søknadstype:

Prosjektperiode:

2005 - 2008

Geografi:

Fagområder:

The principal goal of this project is to explore the use of RNA interference (RNAi) technology in cancer therapy using Tissue Factor (TF) as a target. The project is based upon recent advances in RNAi technology and in our understanding of the role of TF in cancer cell biology. The cloning of TF revealed its apparent receptor configuration with an extracellular domain, a transmembrane domain and a short intracellular tail. This and its high specificity ligand made us hypothesize that TF was a receptor a nd that binding of FVII(a) to TF would trigger intracellular signalling. Formation of the TF/FVIIa complex initiates activation of several signalling pathways including Src-family and MAP kinases, increased transcription of 25 immediate early genes and co ncomitant protein synthesis. RNAi is a natural defense mechanism thought to have evolved to protect organisms from viral diseases. Small interfering RNAs, siRNAs mimic intermediates in the RNAi pathway and serve as sequence specific guides for RNA endonu cleases in cleavage of the complementary mRNA. We have developed highly active and specific siRNAs for the human and murine TF genes. The established as well as planned animal experiments focus upon the use of these siRNAs in various murine tumor models. Specific knockdown of TF in a transformed cell line inhibits the ability of the cells to colonize the lungs after i.v. injection. Can this effect be used to reduce “tumor take”, peroperative dissemination of malignant cells in cancer surgery, or growth of tumor metastases? Does the effect of siRNA on the malignant state of cells indicate a novel, widespread property of cancer cells? Successful results from the proposed project would strongly indicate that a valuable drug against cancer can be developed. The market for such drugs is very large, and if it is possible to obtain good results in preclinical tests, the commercial potential is enormous. The patent situation is highly promising so far.

Budsjettformål:

GNBIO-Grunnleggende næringsrettet bioteknologi

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