Recombination of polynucleotide sequences using random or...

C - Chemistry – Metallurgy – 07 – H

Patent

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C07H 21/04 (2006.01) C12N 9/16 (2006.01) C12N 9/18 (2006.01) C12N 9/56 (2006.01) C12N 9/80 (2006.01) C12N 15/10 (2006.01) C12N 15/31 (2006.01) C12N 15/55 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2285657

A method for in vitro mutagenesis and recombination of polynucleodde sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

L'invention porte sur un procédé in vitro de mutagénèse et de recombinaison de séquences de polynucléotides fondé sur l'extension catalysée par polymérase d'oligonucléotides amorces. Le procédé consiste à amorcer des polynucléotides matrices par des amorces à séquence aléatoire ou définie afin de produire un ensemble de fragments d'ADN à faible niveau de mutations ponctuelles. Lesdits fragments d'ADN subissent ensuite une dénaturation suivie d'une renaturation, puis d'une polymérisation de l'ADN catalysée par enzyme. Le processus est répété un nombre de fois suffisant pour obtenir des gènes de pleine longueur comprenant des mutants des polynucléotides matrices d'origine, lesdits gènes pouvant être par la suite amplifiés par PCR ou clonés en un vecteur en vue de l'expression des protéines codées.

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