Recombinant Dicer-Generated siRNA Reduces Off-Target Effects Compared to Chemically Synthesized siRNAs

Introduction Recombinant Dicer generated siRNA (d-siRNA) has been demonstrated to be as effective as chemically synthesized siRNA (cs-siRNA) at targeted gene knock-down.1 However, many scientists have presumed that d-siRNA will produce significant offtarget gene suppression since there are multiple species of siRNA present in a d-siRNA pool. Yet, no group until recently has investigated whether the opposite might be true, i.e., if d-siRNA would generate fewer nonspecific interactions since the absolute concentration of any individual crossreacting siRNA species within a d-siRNA pool would be relatively negligible. Since some studies have indicated that the off-target effects of cs-siRNA’s are much more prominent than previously assumed2, the question of whether the off-target effects of d-siRNA are greater or lesser than cs-siRNA is highly pertinent given the growing popularity of using siRNA for loss of function studies. A paper appearing in the July 2006 issue of Journal of RNAi and Gene Silencing3 addresses this issue.