Oligonucleotide purification

Discover how WorkBeads resins provide a cost-effective and reproducible purification solution for producing oligonucleotides with high purity and yield. 

Chromatography methods for oligonucleotide purification

The purity of custom-made oligonucleotide preparations produced by solid-phase synthesis can be very high but purification is often required to remove incomplete or erroneous sequences. Anion exchange chromatography is an attractive choice since it can separate the negatively charged oligonucleotides based on length.

For these purifications (including siRNA and mRNA), WorkBeads 40Q has proven to be a superior chromatography resin giving high binding capacity and highly pure oligonucleotides.

Download technical documents and examples


Optimization and scale-up of oligonucleotide purifications

Application note

Purification of oligonucleotides by anion exchange chromatography


Effects of elution conditions in the purification of oligonucleotides by agarose-based anion exchange chromatography


Important optimization parameters for AIEX purifications of 45 nt-long RNA molecules

Application note

Properties of WorkBeads 40 IEX resins: What makes them exceptional?


WorkBeads 40/100 SEC can be used to desalt oligonucleotides and can be cleaned with 1 M NaOH


Conversion of ion-pairing agents/counter ions for oligonucleotides using AIEX.

Application note

Optimization of AIEX purification parameters for phosphorothioate oligonucleotides


The challenge of phosphorothioate oligonucleotide purifications – optimization of AIEX parameters

WorkBeads resins deliver high-yield purification of oligonucleotides

WorkBeads 40Q

WorkBeads 40Q resin is a high-capacity, strong anion exchange resin derivatized with quaternary amine ligands. WorkBeads 40Q resin demonstrates the property of high-resolution separation while giving low backpressure to facilitate purification in bioprocess columns. The agarose-based resin is manufactured using a proprietary method that results in porous beads with a tight size distribution and exceptional mechanical stability. Agarose-based matrices have been successfully used for decades in biotechnology purification, from research to production scale, due to their excellent compatibility with biomolecules, including proteins, peptides, nucleic acids, and carbohydrates. WorkBeads 40Q is highly suitable for the purification of oligonucleotides, giving high purity and good yields. 

Anion exchange chromatography

Since anion exchange chromatography can separate the negatively charged oligonucleotides based on length, it is a commonly used method for oligonucleotide purification. The negatively charged phosphate groups in the nucleic acid backbone are bound to the resin via positively charged groups on the AIEX resin. Generally, the strength of the binding increases with the length of the target. Elution of the adsorbed oligonucleotides can be done by increasing the salt concentration gradient to release the oligonucleotides in the order of increasing length.

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