A facile method for interfering with off-target silencing mediated by the sense strand

Although siRNA duplexes are widely used for gene silencing, several unwanted effects such as activation of innate immunity and off-target gene silencing can limit their therapeutic use. Off-targeting can be identified for both the sense and antisense siRNA strands. Some avenues of obstructing the incorporation of the sense strand into the RNA-induced silencing complex (RISC) are currently being pursued. Herein, a biotin group at the 5'-end of the sense strand was used to inhibit its incorporation into the RISC complex. In contrast to chemical modifications, biotin is a naturally occurring compound and its presence in siRNA sequences will not induce side effects.