Modifying RNAi duplexes (miRNA or siRNA) might alter how the antisense strand interacts with RISC and targets mRNA, impacting functionality. We advise labeling the 5' end of the sense strand for siRNA (or passenger strand for miRNA). Since the 5' end of the antisense (guide) strand is recognized by RISC, add fluorescent modifications to the end of the duplex on the non-interacting strand. You can also compare labeled and non-labeled RNAi duplexes to assess modification effects on siRNA or miRNA functionality.