Overview and recent advances in the purification and isolation of therapeutic oligonucleotides

Abe, Aljaž (author), Časar, Zdenko (author)

Therapeutic oligonucleotides are a novel chemical modality with unique characteristics that offer significant therapeutic potential. With the latest surge in development, they are paving the way to the market at a rapid pace. To support that, scalable and economically sustainable oligonucleotide production is required. The upstream part exploits the well-studied phosphoramidite chemistry, known from the 1960s, using automated synthesis on a solid support. On the other hand, the downstream processing, which consists of purification and isolation steps, has stayed in the shadow of the more thoroughly studied synthesis, even though it is often regarded as the bottleneck of therapeutic oligonucleotide production. Therefore, this review aims to highlight the most important traditional purification and isolation approaches for the production of therapeutic oligonucleotides that ensure product quality, yields, scale, and cost-efficiency as well as newly emerging separation technologies that could become relevant in the future.

• Language: English
• Keywords: biopolymers, purification, preparative chromatography, diazoniumultrafiltration, oligonucleotides, continuous chromatography, ultrafiltration, freeze-drying, chromatography, genetics, impurities
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 15-33
• Numbering: Vol. 29, iss. 1
• PID: 20.500.12556/RUL-166641
• UDC: 615
• ISSN on article: 1083-6160
• DOI: 10.1021/acs.oprd.4c00382
• COBISS.SI-ID: 222989059
• Publication date in RUL: 20.01.2025

Record is a part of a journal

• Title: Organic process research & development
• Shortened title: Org. process res. dev.
• Publisher: American Chemical Society
• ISSN: 1083-6160
• COBISS.SI-ID: 3490842

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Lek d.d., Sandoz Company