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What is a seed sibling control siRNA?

A seed sibling is a siRNA whose seed is a perfect match to an experimental siRNA that gives a phenotype, but has no target in the species of interest. By running a validation study with experimental siRNAs side-by-side with seed siblings, you can determine if the seed alone is active in initiating a phenotype (since it has no known targets) thereby indicating that the phenotype is likely due to a seed-mediated off-target effect. Alternatively, if the seed siblings do not generate a phenotype, there is good indication that the hit was due to knockdown of the intended target and not a seed-based off-target effect.