Methods for nucleic acid manipulation

C - Chemistry – Metallurgy – 12 – Q

Patent

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C12Q 1/68 (2006.01) C12N 9/00 (2006.01) C12N 15/10 (2006.01) C12P 19/34 (2006.01)

Patent

CA 2444649

A method for replicating and amplifying a target nucleic acid sequence is described. A method of the invention involves the formation of a recombination intermediate without the prior denaturing of a nucleic acid duplex through the use of a recombination factor. The recombination intermediate is treated with a high fidelity polymerase to permit the replication and amplification of the target nucleic acid sequence. In preferred embodiments, the polymerase comprises a polymerase holoenzyme. In further preferred embodiments, the recombination factor is bacteriophage T4 UvsX protein or homologs from other species, and the polymerase holoenzyme comprises a polymerase enzyme, a clamp protein and a clamp loader protein, derived from viral, bacteriophage, prokaryotic, archaebacterial, or eukaryotic systems.

L'invention concerne un procédé de réplication et d'amplification d'une séquence d'acide nucléique cible. L'invention concerne également un procédé de formation d'une recombinaison intermédiaire sans dénaturation préalable d'un duplex d'acide nucléique grâce à l'utilisation d'un facteur de recombinaison. Cette recombinaison intermédiaire est traitée au moyen d'une polymérase de haute fidélité afin de permettre la réplication et l'amplification de la séquence d'acide nucléique cible. Selon certains modes de réalisation favoris, la polymérase inclut une holoenzyme polymérase. D'après d'autres modes de réalisation favoris, le facteur de recombinaison est bactériophage de la protéine T4 UvsX ou d'homologues provenant d'autres espèces et l'holoenzyme comprend une enzyme polymérase, une protéine de clamp et une protéine à chargement de clamp, dérivée de systèmes viraux, bactériophages procaryotiques archaébactériens ou eucaryotiques.

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