Chromosomal expression of heterologous genes in bacterial cells

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/90 (2006.01) C12N 15/63 (2006.01) C12N 15/64 (2006.01) C12N 15/65 (2006.01) C12N 15/67 (2006.01)

Patent

CA 2223494

The present invention provides compositions and methods for producing a heterologous protein of interest by inserting a copy of a gene encoding the heterologous protein of interest into the chromosome of a host cell, such as E. coli. A chromosomal transfer DNA (a circular, non-self-replicating DNA) is used to integrate the gene encoding the heterologous protein of interest into the host cell chromosome. The chromosomal transfer DNA comprises at least one selectable marker and may optionally include repeated DNA sequences flanking the selectable marker, facilitating chromosomal amplification of the integrated DNA. The gene encoding the protein of interest may be expressed after integration into the chromosome of the host cell; selection for chromosomal amplification may be performed prior to expression of the gene.

L'invention concerne des compositions et des procédés de production d'une protéine hétérologue, les procédés consistant à insérer une copie d'un gène codant la protéine concernée dans le chromosome d'une cellule hôte telle que E. coli. Un ADN de transfert chromosomique (un ADN circulaire non auto-réplicable) est utilisé pour intégrer le gène codant la protéine hétérologue au chromosome de la cellule hôte. L'ADN de transfert chromosomique comprend au moins un marqueur sélectionnable et éventuellement des séquences d'ADN répétées adjacentes audit marqueur, ce qui facilite l'amplification chromosomique de l'ADN intégré. Le gène codant la protéine selon l'invention peut être exprimé après son intégration dans le chromosome de la cellule hôte; la sélection de l'amplification chromosomique peut s'effectuer avant l'expression du gène.

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