RNA interference induced by siRNAs modified with 4′‐thioribonucleosides in cultured mammalian cells

Short interfering RNAs (siRNAs) variously modified with 4′‐thioribonucleosides against the Photinus luciferase gene were tested for their induction of the RNA interference (RNAi) activity in cultured NIH/3T3 cells. Results indicated that modifications at the sense‐strand were well tolerated for RNAi activity except for full modification with 4′‐thioribonucleosides. However, the activity of siRNAs modified at the antisense‐strand was dependent on the position and the number of modifications with 4′‐thioribonucleosides. Since modifications of siRNAs with 4′‐thioribonucleosides were well tolerated in RNAi activity compared with that of 2′‐O‐methyl nucleosides, 4′‐thioribonucleosides might be potentially useful in the development of novel and effective chemically modified siRNAs.

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