Modified adenoviral vectors for use in gene therapy

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/86 (2006.01) A61K 48/00 (2006.01) C12N 5/10 (2006.01) C12N 7/01 (2006.01) C12N 15/861 (2006.01)

Patent

CA 2384439

The present invention provides means and methods for the generation and manufacturing of recombinant Ad vectors that are modified in E2B and/or E4 functions, preferably, said vectors comprise E1 and/or E2A deletions. For this purpose, the vector genome is modified in the respective promoter regions such that the promoter is only active in a suitable complementing cell line or only active following a certain signal in the case of an inducible promoter. The modified promoter is, on the other hand, inactive under normal conditions, and in normal mammalian and/or human cells. Hence, vectors that possess said modified promoter in the E2B and/or E4 region do not express the respective transcription region in mammalians and/or humans.

L'invention concerne des moyens et des procédés de génération et de fabrication de vecteurs Ad recombinés qui sont modifiés dans des fonctions E2B et/ou E4. Ces vecteurs comportent de préférence des délétions E1 et/ou E2A. A cette fin, le génome du vecteur est modifié dans des régions du promoteur respectives, de façon que le promoteur soit uniquement actif dans une ligne cellulaire complémentaire adéquate ou suivant un certain signal dans le cas d'un promoteur inductible. Le promoteur modifié est, par ailleurs, inactif dans des conditions normales, et dans des cellules mammaliennes et/ou humaines. Ainsi, les vecteurs qui possèdent ce promoteur modifié dans la région E2B et/ou E4, n'expriment pas la région de transcription respective chez les mammifères et/ou les humains.

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