Stability, specificity, and pharmacokinetic properties are some of the challenges facing RNAi therapeutics. In this review, the progresses in chemically modified siRNAs and siRNA conjugates are summarized. The proper modification of siRNA with nucleoside analogues, construction of siRNA conjugates, and reliable prediction of the property based on those strategies for a given siRNA sequence would certainly be an essential part of the solution to these challenges.
