Purification methods for oligonucleotides and their analogs

Details Purification methods for oligonucleotides and their analogs Purification methods for oligonucleotides and their analogs

C - Chemistry, Metallurgy

12

N

C12N 15/10 (2006.01)

Patent

CA 2479901

The present invention discloses methods for separating oligonucleotides from impurities. In the methods of the invention, a target oligonucleotide, in a mixture comprising the target oligonucleotide and an impurity, is separated from the impurity using a titratable anion exchange composition. The target oligonucleotide is bound to the titratable anion exchange composition and an eluting solution which increases in pH over time is passed through the titratable anion exchange composition with the target oligonucleotide bound thereon. Preferably, the eluting solution does not substantially increase its salt concentration. The target oligonucleotide is eluted and thereby separated from the impurity which either elutes at a lower pH or a higher pH than the target oligonucleotide.

L'invention concerne des procédés de séparation d'oligonucléotides et d'impuretés. Selon les procédés de l'invention, un oligonucléotide cible, contenu dans un mélange comprenant ledit oligonucléotide cible et une impureté, est séparé de l'impureté, au moyen d'une composition à échange d'anions, pouvant être titrée. Ledit oligonucléotide cible est lié à la composition à échange d'anions, pouvant être titrée et une solution d'élution, dont le pH augmente dans le temps, s'écoule à travers la composition à échange d'anions liée avec l'oligonucléotide. De préférence, la concentration en sel de la solution d'élution n'augmente pas sensiblement. Ledit oligonucléotide cible est élué puis séparé de l'impureté qui est éluée soit à un pH plus faible soit à un pH plus élevé que ledit oligonucléotide cible.

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