反义核酸药物的合成和纯化

Synthesis and purification of antisense oligonucleotides

反义核酸药物是能与特定mRNA序列互补的不同长度的短小DNA片段,能够通过与靶mRNA形成杂交双链而干扰基因表达。反义核酸药物的合成、纯化是新药临床前评价的基础。本文就国内外反义核酸药物合成中常用的载体、硫代试剂、脱保护试剂的发展,纯化常用的聚丙烯酰胺凝胶电泳、薄层色谱、高效膜吸附色谱、寡核苷酸纯化柱芯和高效液相色谱等方法进行了综述,对其各自的特点、应用前景及优缺点等进行了介绍。

Antisense drugs are synthetic DNA strands that are designed to be complementary to specific mRNA sequences. They can interfere with gene expression by forming duplexes with the target mRNA. Synthesis and purification of antisense drugs are critical for their pre-clinical evaluation. The progress in the development of supports, sulfurization reagents and detritylation reagents for the synthesis and the purification methods applied for antisense drugs such as polyacrylamide gel electrophoresis （PAGE）, thin layer chromatography （TLC）, high efficiency membrane adsorption chromatography, oligonucleotides purification catridge （OPC）, and high performance liquid chromatography （HPLC）was briefly reviewed in the article.