Recombination of polynucleotide sequences using random or...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/10 (2006.01) C12N 9/00 (2006.01) C12N 9/16 (2006.01) C12N 9/56 (2006.01) C12N 9/80 (2006.01) C12N 15/52 (2006.01) C12P 19/34 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2255670

A method for in vitro mutagenesis and recombination of polynucleotide 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 concerne un procédé de mutagenèse in vitro de recombinaison de séquences de polynucléotides sur la base d'une extension catalysée par polymérase d'oligonucléotides amorces. Le procédé consiste à amorcer des polynucléotides matriciels avec des séquences aléatoires ou des amorces à séquences définies afin de produire un ensemble de fragments d'ADN courts présentant un niveau réduit de mutations ponctuelles. Les fragments d'ADN sont soumis à une dénaturation suivie d'une annellation et ensuite une polymérisation d'ADN à catalyse enzymatique. On répète ce procédé un nombre de fois suffisant pour produire des gènes de longueur totale comprenant des mutants des polynucléotides matriciels d'origine. On peut ensuite amplifier ces gènes par amplification en chaîne par polymérase et les cloner en un vecteur d'expression des protéines codées.

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