Off-target effects RNAi - Role of sense-strand (Jun/23/2006 )

Hi there,

I am working with dsRNA to achieve gene silencing by RNAi.
I have heard of "Off-target effects". What happens there and what could be the role of the sense-strand of the dsRNA? If it interacts with DICER could it lead to a degradation of the antisense-strand of the dsRNA?

Thanks.

P.s.: I`ve read a few papers about the interferon response to RNAi. But I am not working with mammalian cells so those kinds of effects are not so interesting for me I guess.

offtargets effects of siRNA are more like activation of interferon response (and see the article of carole sledz for that point) rather than targeting others mRNA sequences.
role of the sense strand is not that clear. Some hypothesis are mentionning the fact that during recognition of terget RNA, a triple helix involving sense, anti sense and target RNA occur.

The interferon response is definitely an off-target effect of RNAi, although current siRNA protocols have attempted to overcome this response through the use of shorter RNA oligos. shRNA, as far as I know, won't trigger an interferon response and is thus a preferred solution to this problem.

There are however other off-target responses attributed to siRNA. Matches to the 3' UTR of endogenous RNAs may account for some of these effects. One paper describing this phenomenon is attached.