> These are similar, but very different applications--antiviral response or gene silencing. The fears that you cite refer to gene silencing, not to the antiviral response. Remebee has only to do with the antiviral response.

What I am talking about is the ramifications of feeding synthetic RNA as a therapeutic tool. What is the potential effect of this? The RNA may be intended to interfere only with the targeted virus' replication, but the literature is peppered with reports of unforeseen side effects. To wit:

> recent evidence suggests that over-dosing RNAi can have detrimental side effects on cells and tissues, and cause toxicities and lethalities in small animals. Unlike previously noted adverse effects, these new phenomena are unrelated to RNAi sequences but rather involve saturation of cellular gene silencing pathways. Considering the importance of these alarming findings for the clinical translation of RNAi technologies, we review the underlying mechanisms and discuss potential solutions.

> we focus on a conclusion from the most recent studies, namely, that the potential benefit from RNAi is also associated with intrinsic risks. Among these, two particular concerns are (1) the induction of an immune response, a risk that is specifically inherent to ectopic siRNAs that can be detected by cellular sensors of foreign nucleic acids, such as toll-like receptors and (2) off-targeting, defined as unwanted knockdown of genes besides the actual target, potentially resulting in fatal consequences for the cell and tissue, such as cytotoxicity.

> we discuss a third concern common to all three RNAi inducers that has only become apparent in the very recent past, namely, toxicity from over-dosing.

Use of small RNAs for therapeutic gene silencing: risk versus benefit. 
Drug Discovery Today: Technologies | Mechanistic pharmacology, new developments	Vol. 7, No. 1 2010

* * *

> While emerging data suggest RNAi treatment to be effective and well tolerated and thus spur tremendous optimism, there are also escalating somber reports in animals of severe adverse side effects from in vivo RNAi. This is further underscored by notions that even marginal RNAi toxicities can cause detrimental effects, such as increased emergence of viral resistance 

Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence
The Journal of Clinical Investigation Volume 120 Number 9 September 2010

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