Bone sialoprotein based toxic gene therapy for the treatment...

A - Human Necessities – 01 – N

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A01N 43/04 (2006.01) A61K 38/45 (2006.01) A61K 48/00 (2006.01) C07H 21/04 (2006.01) C07K 14/47 (2006.01) C12N 15/63 (2006.01) C12N 15/85 (2006.01) C12N 15/861 (2006.01)

Patent

CA 2355228

The present invention relates to promoters, enhancers and other regulatory elements that direct expression within tumor and tissue cells with calcification potential. In particular, it relates to compositions comprising nucleotide sequences from the 5' regulatory region, and transcriptionally active fragments thereof, that control expression of a bone sialoprotein ("BSP"). Specifically provided are expression vectors, host cells and transgenic animals wherein a BSP regulatory region is capable of controlling expression of a heterologous coding sequence, over-expressing an endogenous BSP coding sequence or an inhibitor of a pathological process or knocking out expression of a specific gene believed to be important for a calcification- related disease in tumor and tissue cells with calcification potential. The invention also relates to methods for using said vectors, cells and animals for screening candidate molecules for agonists and antagonists of disorders involving tumor and tissue cells with calcification potential. The present invention further relates to compositions and methods for modulating expression of compounds within tumor and tissue cells with calcification potential. Methods for using molecules and compounds identified by screening assays for therapeutic treatments also are provided. The invention further relates to methods of treating tumors and other diseases and disorders involving tumor and tissue cells with calcification potential.

L'invention concerne des promoteurs, des amplificateurs et d'autres éléments régulateurs qui dirigent l'expression d'un potentiel de calcification dans des cellules tissulaires ou tumorales. L'invention concerne, tout particulièrement, des compositions comprenant des séquences nucléotidiques de la région régulatrice 5', et des fragments de celle-ci actifs sur le plan transcriptionnel qui régulent l'expression d'une sialoprotéine osseuse (BSP). Plus spécifiquement, l'invention concerne des vecteurs d'expression, des cellules hôtes et des animaux transgéniques dans lesquels la région régulatrice de BSP est capable de réguler l'expression d'une séquence de codage hétérologue, de surexprimer une séquence codant pour une BSP endogène ou un inhibiteur de processus pathologique, ou d'exprimer par knock-out un gène spécifique que l'on croit responsable d'une maladie liée à une calcification dans des cellules tissulaires ou tumorales à potentiel de calcification. L'invention concerne également des techniques utilisant lesdits vecteurs, cellules et animaux dans le criblage permettant d'identifier des molécules candidates agonistes ou antagonistes de troubles affectant des cellules tissulaires et tumorales à potentiel de calcification. L'invention concerne également des compositions et des techniques permettant de moduler l'expression de composés dans des cellules tissulaires et tumorales à potentiel de calcification. L'invention concerne, en outre, des techniques d'utilisation des molécules et des composés identifiés par criblage pour des traitements thérapeutiques. L'invention concerne enfin des techniques de traitement des tumeurs et autres troubles ou maladies impliquant des cellules tissulaires ou tumorales à potentiel de calcification.

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