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Intracellular Methylases Delivery as therapeutic tool for carcinoma specific regulation of Gene expression.

Objetivo

The goal of this CRAFT consortium is the generation of a prototype of a new generation of drugs, which are based on the combination of established technologies in the field of protein engineering, DNA-targeting and drug delivery. The combination of the diverse fields of technology is very innovative and a reachable task. As prototype we aim for a double targeted therapeutic compound which is a carcinoma cell specific delivered and carcinoma gene specific in his DNA-methyltransferase activity which can switch the expression of a tumour-associated gene involved in carcinogenesis expressed in 40% of all human tumours, from on to off. Cancer is the second cause of death in the Western world and continues to emerge at an accelerated rate in the developing countries as well. Although progress has been made in the therapy of some types of cancer, the overall survival prognosis with current standard therapy is poor. Therefore, new treatment strategies are needed. The approach we propose here is based on the selective silencing of the epithelial glycoprotein-2 (EGP-2) gene, which is abundantly expressed in a variety of carcinomas, counting for 40% of all cancers. The goal of the proposed method is to selectively silence the EGP-2 gene by targeted methylation of the EGP-2 promoter. The therapeutic compounds we wish to develop consist of a targeted DNA methyltransferase and a targeted delivery system, based on synthetic amphiphiles, specific for EGP-2 positive cells. The targeted DNA-methyltransferase is a covalent complex of a triplex forming oligonucleotide (TFO) and the CpG-specific DNA methyltransferase M.SssI. This TFO-M.SssI conjugate has the potential to methylate a unique CpG site in a genome. Because of the high targeting specificity of the envisaged product, the proposed approach is expected to be free of many negative side effects, and thus can lead to a more effective treatment of a broad-range of cancers.

Convocatoria de propuestas

FP6-2003-SME-1
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Régimen de financiación

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Coordinador

SYNVOLUX THERAPEUTICS BV
Aportación de la UE
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Dirección
L.J. Zielstraweg 1
GRONINGEN
Países Bajos

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Participantes (5)