Synthesis of 21 nt siRNAs bearing chemically modified dangling ends with a novel nucleobase was achieved. Evaluation of gene silencing of bcr-abl chimeric gene derived from Philadelphia chromosome by thus obtained chemically modified siRNAs was performed using human leukaemia cell line K-562 and resulted in efficient suppression of the targeted gene. siRNAs whose sense strands were modified with a novel base were found to be more effective than a native siRNA and that siRNAs whose antisense strands were modified with a novel base showed largely decreased silencing effects on the contrary.