Plasmid production and expression of recombinant proteins in...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/63 (2006.01) C12N 15/64 (2006.01) C12N 15/65 (2006.01)

Patent

CA 2697498

The invention relates to a mutated cell such as a bacteria or yeast in which the thyA gene coding thymidylate synthase includes a nonsense codon, preferably the amber codon, said nonsense codon replacing a codon coding an amino acid and inducing the interruption of thyA gene translation and the auxotropy of the cell for the thymidine. Advantageously, the endA gene coding the endonuclease 1 and/or the recA gene coding the recombinase is inactivated in said mutated cell. The invention also relates to an expression plasmid including a transgene and a sequence of a suppressing ARM structural gene containing an anticodon that can be paired with the nonsense codon of the thyA gene and is specific of an amino acid capable of restoring the translation of the mutated thyA gene and thereby obtaining a protein of the wild or mutated type having a thymidylate synthase activity. The invention also relates to a method for the multiplication of the expression plasmid.

La présente invention concerne une cellule mutée telle qu'une bactérie ou une levure, dans laquelle le gène thyA codant la thymidylate synthase comporte un codon non sens, de préférence le codon ambre, ledit codon non sens remplaçant un codon codant un acide aminé et entraînant un arrêt de la traduction du gène thyA et l'auxotrophie de la cellule pour la thymidine. Avantageusement, le gène endA codant l'endonucléase 1 et/ou le gène recA codant la recombinase est inactivé dans ladite cellule mutée. L'invention concerne également un plasmide d'expression comprenant un transgène et une séquence de gène structural d'ARM suppresseur comprenant un anticodon capable de s'apparier au codon non sens du gène thyA et qui est spécifique d'un acide aminé capable de restaurer la traduction du gène thyA muté et d'obtenir ainsi une protéine de type sauvage ou mutée possédant une activité thymidylate synthase. Un procédé de multiplication du plasmide d'expression est également revendiqué.

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