液相寡核苷酸合成:过去,现在和未来的预测。

Q4 Chemistry
Current Protocols in Nucleic Acid Chemistry Pub Date : 2019-06-01 Epub Date: 2019-03-28 DOI:10.1002/cpnc.82
Alejandro Gimenez Molina, Yogesh S Sanghvi
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引用次数: 20

摘要

治疗性寡核苷酸已成为一种强大的范例,具有治疗多种人类疾病的能力。因此,我们已经见证了超过一百种寡核苷酸目前正在积极的临床试验和八种食品和药物管理局(FDA)批准的药物。迄今为止,传统的固相合成方法已经有效地满足了对寡核苷酸类药物的需求。然而,有些产品在临床试验的后期阶段,预计在不久的将来会有大量的公吨需求。因此,这些产品的大规模生产已成为工艺化学家的当务之急。本文综述了液相寡核苷酸合成(LPOS)技术的研究进展,作为一种可能的替代策略来应对规模挑战。介绍了在开发LPOS技术方面的主要努力的文献综述。令人欣慰的是,目前正在进行认真的尝试,以开发一种有效的环境友好的绿色化学方案,这种方案可扩展且具有成本效益,用于制造寡核苷酸。本文总结了最具创新性的LPOS方案,以提供未来大规模生产寡核苷酸的可能性。©2019 by John Wiley & Sons, Inc。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Liquid-Phase Oligonucleotide Synthesis: Past, Present, and Future Predictions.

Therapeutic oligonucleotides have emerged as a powerful paradigm with the ability to treat a wide range of the human diseases. As a result, we have witnessed more than one hundred oligonucleotides currently in active clinical trials and eight Food and Drug Administration (FDA)-approved drugs. Until now, the demand for oligonucleotide-based drugs has been fulfilled by conventional solid-phase synthesis in an effective manner. However, there are products in advanced stages of clinical trials projecting a collective demand of metric ton quantities in the near future. Therefore, large-scale manufacturing of these products has become a high priority for process chemists. This article summarizes the advances in liquid-phase oligonucleotide synthesis (LPOS) as a possible alternative strategy to meet the scale-up challenge. A review of the literature describing major efforts in developing LPOS technologies is presented. Gratifyingly, serious attempts are under way to develop an efficient environmentally benign green chemistry protocol that is scalable and cost effective for the manufacturing of oligonucleotides. A summary of the most innovative LPOS protocols has been included to provide a glimpse of what may be possible in the future for large-scale production of oligonucleotides. © 2019 by John Wiley & Sons, Inc.

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来源期刊
Current Protocols in Nucleic Acid Chemistry
Current Protocols in Nucleic Acid Chemistry Chemistry-Organic Chemistry
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期刊介绍: Published in association with International Society for Nucleosides, Nucleotides & Nucleic Acids (IS3NA) , Current Protocols in Nucleic Acid Chemistry is equally valuable for biotech, pharmaceutical, and academic labs. It is the resource for designing and running successful research projects in the rapidly growing and changing field of nucleic acid, nucleotide, and nucleoside research.
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