RNAi is a natural system evolved by organisms to inhibit gene expression, either by cleaving a particular RNA or inhibiting the translation of a particular RNA. The RISC complex binds to a small strand of RNA and uses this strand to find target mRNA. Once it binds to a target strand it either cleaves the strand (if it is mostly complementary) or inhibits the translation of the strand (if it is partially complementary). This system was thought to have been selected for as it putatively provides several services to the cell: antiviral defense and regulation of gene expression.

These pieces of RNA are not stopping reactions from occurring at certain enzymes; rather, they are stopping the synthesis of certain enzymes (granted, with the enzymes missing the reactions will be stopped).

Once the system was discovered, it was exploited as a means to experimentally silence the expression of genes. A large industry has grown around synthetic exogenous RNA molecules like siRNA, shRNA and other RNAi strategies.

There are several drawbacks to the siRNA approach for gene silencing. These include modulation of the expression of unintended partially-complementary mRNAs and activation of an innate immune response by binding of double-stranded RNA to Toll-like receptors.