Self-regulated apoptosis of inflammatory cells by gene therapy

Details Self-regulated apoptosis of inflammatory cells by gene therapy Self-regulated apoptosis of inflammatory cells by gene therapy

C - Chemistry, Metallurgy

12

N

C12N 15/85 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) C12N 5/10 (2006.01) C12N 9/64 (2006.01) C12Q 1/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2321178

This invention relates to chimeric nucleic acids and to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells the chimeric nucleic acid. The chimeric nucleic acid having at least one TNF.alpha. promoter enhancer attached to a functional copy of a TNF.alpha. promoter and further attached to at least one copy of an apoptosis-inducing gene, which is further attached to a 3'UTR. The apoptosis-inducing gene is Granzyme B. The invention also relates to methods of making and using self-regulated apoptosis chimeric nucleic acids and pharmaceutical compositions containing them for treating inflammatory diseases.

L'invention concerne des acides nucléiques chimères et l'induction thérapeutique de l'apoptose dans des cellules inflammatoires activées, ou dans des cellules se trouvant sur un site d'inflammation, par introduction dans ces cellules de cet acide nucléique chimère. L'acide nucléique chimère comporte au moins un activateur du promoteur du TNF.alpha. fixé à une copie fonctionnelle d'un promoteur du TNF.alpha., ainsi qu'à au moins une copie d'un gène induisant l'apoptose, lequel est ensuite fixé à une région 3'UTR. Le gène induisant l'apoptose est Granzyme B. L'invention concerne également des méthodes de production et d'utilisation d'acides nucléiques chimères d'apoptose autorégulée, et des compositions pharmaceutiques les renfermant destinées au traitement de maladies inflammatoires.

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