Synthesis and evaluation of modified siRNA molecules containing a novel glucose derivative

Chemical modifications are critical for the development of safe and effective siRNAs for downstream applications. In this study, we report the synthesis of a novel glucose phosphoramidite, a triazole-linked to uracil at position one, for incorporation into oligonucleotides. Biological testing revealed that the glucose derivative at key positions within the sense or antisense strand can lead to potent gene-silencing activity, thus highlighting its tolerance in both sense and antisense positions. Furthermore, the A-form helical formation was maintained with this modification. Overall, placing the modification at the 3 ' end and at key internal positions led to effective RNAi gene-silencing activity.

Automated summary

Chemical modifications in siRNAs, such as a novel glucose derivative reported in this study, can lead to potent gene-silencing activity and tolerance in both sense and antisense positions. Maintaining A-form helical formation and placing the modification at specific positions resulted in effective RNAi gene-silencing activity.