Methods of synthesizing polynucleotides by ligation of...

C - Chemistry – Metallurgy – 12 – Q

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

Patent

CA 2304258

Methods of synthesizing polynucleotides are disclosed involving the simultaneous ligation of a set of oligomer 5'-phosphates onto a template-bound primer. The set of these oligomers can be preselected to contain oligomers which are complementary to the template strand or the oligomers can be supplied as a library and allowed to self select. The synthesis by ligation can proceed unidirectionally or bidirectionally from the primer and can be used to synthesize both strands simultaneously by the use of two primers. The ligation is preferably performed with a ligase enzyme. The methods of synthesis are useful in a variety of applications, including cloning, amplification, labeling, diagnostic assays, mutation analysis and screening, gene expression monitoring and sequence analysis.

La présente invention concerne des procédés de synthétisation de polynucléotides qui font intervenir la ligature simultanée de 5'-phosphates oligomères sur une amorce lié à une matrice. L'ensemble de ces oligomères peut être présélectionné de manière à renfermer des oligomères complémentaires du brin de la matrice, ou bien les oligomères peuvent être fournis sous forme de bibliothèque et s'autosélectionner. La synthèse par ligature peut découler unidirectionnellement ou bidirectionnellement de l'amorce et servir a synthétiser simultanément les deux brins au moyen de deux amorces. La ligature se fait de préférence avec une ligase. Ces procédés de synthèse sont utiles à maints égards, notamment en matière de clonage, d'amplification, de marquage, de dosage à des fins de diagnostic, d'analyse de mutation et de criblage, de surveillance de l'expression des gènes et d'analyse de séquences.

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