"The “dirtiness” will depend on the extent to which VEGF is needed for normal retinal functioning."
I would argue that the "dirtiness" may extend beyond VEGF-specific effects. I don't think RNAi is necessarily more specific than a good ligand. One case in point:
Beyond this obvious problem, there may be others. Don't get me wrong, I think RNAi is useful; but its specificity is basically assumed (ie not adequately tested). For starters, consider that many promotors are bidirectional, many transcripts are antisense or pseudogene, and the central dogma of DNA=>RNA=>Protein is probably oversimplified. Indeed, the number of mRNA transcripts vastly outnumbers both genes and proteins. Furthermore, even when an si is specific for a mRNA transcript, if that mRNA (or any of its fragments) has multiple functions beyond encoding protein, how can its degradation be specific?
At any rate, there is a developing trend in my environment to question the specificity of RNAi. We just don't yet understand all the cellular functions of RNA.
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