固相合成是,到目前为止,制造寡核苷酸的首选方法,数量从几微克用于研究目的到几公斤用于治疗或商业用途。但是对于大规模的寡核苷酸制造,扩大规模和危险废物生产带来了挑战,需要研究替代合成技术。尽管玻璃支架有缺点,使用可溶性载体作为替代物存在困难,因为它们具有高的总产率和复杂的纯化步骤。为了应对这些挑战,已经开发了各种独立的方法;然而,例如循环效率不足和所需长度的寡核苷酸链的合成等问题继续存在。在这项研究中,我们回顾了当前的发展,优势,以及最近报道的基于受控孔隙玻璃的载体替代品的困难,并讨论支持选择解决寡核苷酸合成过程中出现的问题的重要性。
Solid-phase synthesis is, to date, the preferred method for the manufacture of oligonucleotides, in quantities ranging from a few micrograms for research purposes to several kilograms for therapeutic or commercial use. But for large-scale
oligonucleotide manufacture, scaling up and hazardous waste production pose challenges that necessitate the investigation of alternate synthetic techniques. Despite the disadvantages of glass supports, using soluble supports as a substitute presents difficulties because of their high overall yield and complex purification steps. To address these challenges, various independent approaches have been developed; however, other problems such as insufficient cycle efficiency and synthesis of
oligonucleotide chains of desired length continue to exist. In this study, we present a
review of the current developments, advantages, and difficulties of recently reported alternatives to supports based on controlled pore glass, and discuss the importance of a support choice to resolve issues arising during
oligonucleotide synthesis.