{"id":1939,"date":"2025-12-03T13:38:10","date_gmt":"2025-12-03T13:38:10","guid":{"rendered":"https:\/\/www.chromacon.com\/?post_type=application&p=1939"},"modified":"2026-05-12T14:30:04","modified_gmt":"2026-05-12T12:30:04","slug":"oligonucleotides","status":"publish","type":"application","link":"https:\/\/www.chromacon.com\/en\/applications\/oligonucleotides\/","title":{"rendered":"Oligonucleotides"},"content":{"rendered":"
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\n Oligonucleotides <\/p>\n \n

\n More Oligo<\/strong>. Fewer IPCs. MCSGP for ASOs, siRNAs & GalNAc Conjugates.\n <\/h1>\n \n
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In AIEX or IP-RP modes. Recover full-length product that batch chromatography discards in side-fractions, without changing your resin, gradient, or buffers.<\/p>\n

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Published case results: +50%<\/strong> yield (60\u219290%+) on 20-mer | +38.8 pp<\/strong> yield (52.7\u219291.5%) on GalNAc conjugate | +13 pp<\/strong> yield (80\u219293%) on conjugated siRNA AIEX<\/p>\n

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Sources: YMC ChromaCon Oligo Application Note; Weldon et al., J. Chromatogr. A 2022; Weldon et al., Org. Process Res. Dev. 2025<\/em><\/strong><\/p>\n <\/div>\n <\/div>\n\n

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\n Talk to Our Oligonucleotide Specialists<\/span><\/a><\/span> <\/div>\n
\n Download the Application Note<\/span><\/a><\/span> <\/div>\n <\/div>\n <\/div>\n <\/div>\n\n
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\n Talk to Our Oligonucleotide Specialists<\/span><\/a><\/span> <\/div>\n
\n Download the Application Note<\/span><\/a><\/span> <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n
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\n The Oligonucleotide Purification Bottleneck <\/h2>\n \n
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Oligonucleotide therapeutics are surging \u2014 with 24 FDA-approved drugs, 200+ candidates in clinical trials, and blockbuster siRNAs driving demand to multi-kilogram scales. Purification by anion exchange (AIEX) or ion-pair reversed-phase (IP-RP) chromatography is the critical downstream bottleneck.<\/p>\n

Batch chromatography forces a painful trade-off: high purity or high yield \u2014 not both.<\/strong> Oligonucleotide crude feeds contain hundreds of closely related impurities \u2014 N-1 shortmers, N+1 longmers, phosphodiester (PO) failures, depurination products, and phosphorothioate diastereomers \u2014 many differing by as little as 1 Da in a 7,000+ Da molecule. Achieving target purity requires a narrow center-cut, discarding valuable full-length product in side-fractions. Recovering that product means costly re-chromatography \u2014 with all the associated solvent, buffer, and QC burden.<\/p>\n

For high-volume APIs demanded by cholesterol-lowering siRNAs, hepatitis B ASOs, and GalNAc-conjugated therapies, this inefficiency is unsustainable.<\/p>\n <\/div>\n \n <\/div>\n\n

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\n The Solution: MCSGP with AutoPeak\u00ae for Oligonucleotide Purification <\/h2>\n \n
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MCSGP (Multi-column Countercurrent Solvent Gradient Purification) eliminates the purity-yield trade-off in oligonucleotide chromatography. Two identical columns continuously recycle impure side-fractions \u2014 recovering full-length oligonucleotide product that batch processes discard. It uses the same AIEX, IP-RP, and RP resins, buffers, and solvents<\/strong> as your existing batch oligonucleotide method.<\/p>\n

AutoPeak\u00ae dynamic process control monitors oligonucleotide elution profiles in real-time via UV and conductivity, automatically adjusting collection windows to maintain consistent output quality \u2014 enabling robust, unattended 24\/7 oligonucleotide purification. Without AutoPeak\u00ae control, studies have shown yields can drop to as low as 20% under process variability \u2014 AutoPeak\u00ae eliminates this risk.<\/p>\n

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Same chemistry. Better results.<\/strong> MCSGP works with the AIEX, IP-RP, and RP stationary phases and mobile phases already used in your oligonucleotide batch process \u2014 your existing resin and eluent conditions are the starting point for MCSGP development. No change to your chromatographic chemistry is needed.<\/p>\n<\/blockquote>\n <\/div>\n \n Learn About MCSGP + AutoPeak\u00ae<\/span><\/a><\/span> <\/div>\n\n

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Proven Results: MCSGP vs. Batch – Oligonucleotide Purification<\/h2>\n\n\n\n
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\n +13\u201374% <\/h2>\n \n

\n Yield Increase <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n\n\n\n

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\n 90%+ <\/h2>\n \n

\n Typical MCSGP Yield <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n\n\n\n

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\n 87% \u2191 <\/h2>\n \n

\n Throughput Increase <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n<\/div>\n\n\n\n

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\n Zero <\/h2>\n \n

\n Re-chromatography Runs <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n\n\n\n

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\n 42.5% \u2193 <\/h2>\n \n

\n Synthesis Scale Reduction <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n\n\n\n

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\n 2\u00d7 <\/h2>\n \n

\n Productivity Gain <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n<\/div>\n\n\n

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