Overview and Recent Advances in the Purification and Isolation of Therapeutic Oligonucleotides

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2024-12-16 DOI:10.1021/acs.oprd.4c00382

Aljaž Abe, Zdenko Časar

引用次数: 0

Abstract

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.

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治疗性寡核苷酸是一种新型化学模式，具有独特的特性，具有巨大的治疗潜力。随着最新研发成果的涌现，寡核苷酸正在快速进入市场。为此，需要可扩展且经济上可持续的寡核苷酸生产。上游部分利用的是早在 20 世纪 60 年代就已熟知的亚磷酰胺化学，在固体支持物上进行自动合成。另一方面，由纯化和分离步骤组成的下游处理过程，虽然经常被认为是治疗性寡核苷酸生产的瓶颈，但却一直处于研究更为透彻的合成过程的阴影之下。因此，本综述旨在重点介绍用于生产治疗性寡核苷酸的最重要的传统纯化和分离方法，这些方法可确保产品质量、产量、规模和成本效益，同时还介绍了未来可能会出现的新兴分离技术。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.

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