Methods to enhance and confine expression of genes

A - Human Necessities – 61 – K

Patent

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Details

A61K 48/00 (2006.01) A61K 38/17 (2006.01) A61K 38/19 (2006.01) C12N 15/63 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2340929

The present invention provides a novel approach to gene therapy of restricted areas such as tumors. The methods introduced here comprise: (a) placing a gene of interest in a plasmid vector driven by a heat or light inducible promoter; (b) modifying this vector by including a tetracycline responsive fusion protein which acts as a transcriptional activator, thus permitting regulation of gene expression by varying the levels of drug and; (c) modifying this vector by including DNA sequences that reduce or eliminate expression of genes in normal bystander cells. Also provided are a set of vectors for both sustained and regulable expression. There is also presented novel vectors for the gene therapy treatment of local and metastatic breast, ovarian and prostate cancer.

La présente invention concerne une nouvelle approche de thérapie génique appliquée à des zones restreintes telles que des tumeurs. La démarche décrite ici consiste à: (a) placer un gène d'intérêt dans un vecteur plasmidique entraîné par un promoteur inductible par la chaleur ou par la lumière; (b) modifier ce vecteur par inclusion d'une protéine de fusion sensible à la tétracycline et agissant comme activateur de transcription, ce qui permet de réguler l'expression du gène en jouant sur la concentration du médicament et; (c) modifier ce vecteur en incluant des séquences d'ADN qui réduisent ou suppriment l'expression de gènes dans des cellules normales de voisinage. L'invention concerne aussi un ensemble de vecteurs à expression tant continue que régulable. Sont également décrits de nouveaux vecteurs destinésà la thérapie génique des cancers du sein, des ovaires et de la prostate, localisés ou métastatiques.

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