Method for selecting recombinase variants with altered...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/52 (2006.01) C12N 9/00 (2006.01) C12N 9/22 (2006.01) C12N 15/10 (2006.01) C12Q 1/25 (2006.01)

Patent

CA 2367396

Disclosed are variants of Cre recombinase that have broadened specificity for the site of recombination. Specifically, the disclosed variants mediate recombination between sequences other than the loxP sequence and other lox site sequences on which wild type Cre recombinase is active. In general, the disclosed Cre variants mediate efficient recombination between lox sites that wild type Cre can act on (referred to as wild type lox sites), between variant lox sites not efficiently utilized by wild type Cre (referred to as variant lox sites), and between a wild type lox site and a variant lox site. Also disclosed are methods of recombining nucleic acids using the disclosed Cre variants. For example, the disclosed Cre variants can be used in any method or technique where Cre recombinase (or other, similar recombinases such as FLP) can be used. In addition, the disclosed Cre variants allow different alternative recombinations to be performed since the Cre variants allow much more efficient recombination between wild type lox sitsites and variant lox sites. Control of such alternative recombination can be used to accomplish more sophisticated sequential recombinations to achieve results not possible with wild type Cre recombinase.

L'invention concerne des variantes de recombinase Cre augmentant la spécificité du site de recombinaison. Plus particulièrement, l'invention concerne des variantes servant de médiation dans la recombinaison entre des séquences autres que la séquence loxP et autres séquences du site lox sur lesquelles la recombinase Cre de type sauvage est active. En général, les variantes Cre de l'invention servent de médiation dans la recombinaison efficace entre les sites lox sur lesquels peut agir la Cre de type sauvage (désignés sous le nom de sites lox de type sauvage), entre des sites lox variants n'étant pas utilisés de manière efficace par la Cre de type sauvage (désignés sous le nom de sites lox variants), et entre un site lox sauvage et un site lox variant. L'invention concerne également des méthodes de recombinaison d'acides nucléiques à l'aide des variantes Cre de l'invention. Par exemple, ces variantes Cre peuvent être utilisées dans toute méthode ou technique dans lesquelles peut être utilisée la recombinase Cre (ou d'autres recombinases semblables telles que la FLP). De plus, les variantes Cre permettent d'effectuer des recombinaisons diverses. En effet, les variantes Cre permettent une recombinaison beaucoup plus efficace entre les sites lox de type sauvage et les sites lox variants. La commande d'une recombinaison de ce type permet de réaliser des recombinaisons séquentielles plus sophistiquées et d'obtenir des résultats impossibles à atteindre avec la recombinase Cre de type sauvage.

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