The Secret To Pure Oligos: Why Anion Exchange Chromatography Rules At Scale

Moving from crude synthesis to a pure therapeutic candidate requires a purification strategy that does not falter during scale-up. In the seventh installment of the Oligos Made Easy series, we examine why anion exchange chromatography (AEX) remains a dominant method for large-scale production. Beyond its high loading capacity and eco-friendlier aqueous buffers, AEX offers the robust separation efficiency required for GMP manufacturing.

We break down the practicalities of purifying oligo(dT) on a liter scale—demonstrating how to achieve 95% purity with excellent yield—and discuss critical technical nuances, such as selecting the right counterions to protect stainless steel equipment. While AEX is powerful, it is not without hurdles; understanding how to mitigate issues like secondary structure aggregation and endotoxin risks is essential for a successful process.