Application of 4'--α-aminoethoxy-2'--methyl-5-propynyl-uridine for antisense therapeutics.

Owing to the increased public interest and advances in chemical modifications, the approval of antisense therapeutics, a class of mRNA-targeting DNA-based oligonucleotide therapeutics, has accelerated in recent years. It was previously reported that siRNAs with several 4'--α-aminoethoxy-2'--methyl-uridine (4AEoU) analogs could maintain moderate thermal stability similar to the native ones while showing robust nuclease stability. In this study, we further expanded the application of 4AEo modification to antisense therapeutics and achieved superior thermal stability by adding the uracil 5-propynyl modification.

Non-terminal conjugation of small interfering RNAs with spermine improves duplex binding and serum stability with position-specific incorporation.

The conjugation of small interfering RNAs (siRNAs) has been studied using lipid and ligand conjugates for efficient delivery. However, most conjugates have been inserted at the terminal position; very few have been inserted at non-terminal positions. Herein, we synthesized a 4'--propyllevulinate-2'--methyluridine analog for non-terminal conjugation of spermine into the passenger strand of siRNA.