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Why am I seeing non-specific knock-down?

Keep in mind that other associated or downstream genes can play a role in non-specific knock-down. Ensure that you are using positive and negative controls. Also bear in mind that some genes have mRNA that stays in the cell for a longer period of time than other genes. This can affect the time it takes to observe gene knock-down. Another option is that the gene may be temporally expressed, which can cause a false-positive for knock-down.