化学修饰对寡核苷酸生物活性的影响

The effect of chemical modification on the biological activity of oligonucleotide

寡核苷酸可根据碱基互补原则特异性地与靶基因或 m RNA结合 ,从基因复制、转录、m RNA剪接、转运或转译等水平上抑制目的基因的表达 ,从而实现基因调控。其生物功能在很大程度上取决于它的稳定性、生物利用度及与靶基因结合或反应的特性。通过特定的化学修饰可改变寡核苷酸的物理、化学特性 ,其中利用一些活性基团- DNA嵌入剂与寡核苷酸偶联修饰是非常重要和行之有效的修饰方法 ,能有效地提高寡核苷酸的生物功能。

Oligonucleotides have the ability to selectively block target gene and mRNA according to base-pair complementary binding at the process of replication and transcription of DNA, cutting, transfer or translation of mRNA, and thereby may become the kind of perfect therapeutic agents at genetic level. The biological activities of oligonucleotides depend mainly on their stabilization to nucleases, biological ingestion and specificity of combining or interaction with target gene.These physical and chemical properties of oligonucleotides can be improved by specific modification.It is a significantly important and potent method in which oligonucleotides are covalently linked to DNA intercalating agents or other chemical substitutes, resulting in effective improvement of biological activities of oligonucleotides.