I'm not a "doubter" of RNAi utility. I do however have a healthy scepticism regarding the specificity of RNAi, which is often assumed (incorrectly) to be nearly perfect.
The potential for "off target" regulation heightens the risk of side effects due to RNAi, and complicates studies that use RNAi to probe gene function. One interesting thing I have heard through the grape vine is that a single miRNA can inhibit up to 10% of the geneome! miRNA's are endogenous, and this (as well as other) finding suggests the existence of a complex and unexpected signal transduction mechanism, which occurs on the mRNA level to coordinate gene expression. It's really not that surprising, given that the cell utilizes elaborate machinery for processing small RNA's (Dicer, RISC, etc.).
Clearly, it is not as simple as binding to complimentary sequences and squelching gene expression.
Cheers
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