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We invented a method of making siRNAs directly from bacterial cells.This method utilizes p19 siRNA binding protein, found in a plant RNA virus, which stabilizes a cryptic bacterial siRNA-like RNA species (named pro-siRNAs for prokaryotic siRNAs).pro-siRNAs can be engineered to target any gene and are as effective as synthetic siRNAs without immunogenicity or offtarget effect.Furthermore pro-siRNAs, as a pool of multiple siRNAs targeting the same gene, could be particularly suitable for suppressing more variable viral and oncogenic genes.We envision pro-siRNA could become a valuable and cost-effective tool for a wide range of RNAi applications.