RNA Interference (RNAi) is a potential RNA based therapy that can be used to silence the effects of specific genes. The RNAi process makes use of a pathway that exists in most cells as a defense mechanism against foreign genetic material. Since this pathway is found in both eukaryotic and prokaryotic cells, it probably evolved before the evolutionary split in these two cell types.

RNA interference (RNAi) is a system within living cells that helps to control which genes are active and how active they are. Two types of small RNA molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference. RNAs are the direct products of genes, and these small RNAs can bind to specific other RNAs and either increase or decrease their activity.

RNAi is an RNA-dependent gene silencing process that is controlled by the RNA-induced silencing complex (RISC) and is initiated by short double-stranded RNA molecules in a cell's cytoplasm, where they interact with the catalytic RISC component argonaute. When the dsRNA is exogenous (coming from infection by a virus with an RNA genome or laboratory manipulations), the RNA is imported directly into the cytoplasm and cleaved to short fragments by the enzyme dicer.

RNA interference has been used for applications in biotechnology, particularly in the engineering of food plants that produce lower levels of natural plant toxins. Such techniques take advantage of the stable and heritable RNAi phenotype in plant stocks.

The discovery of RNAi was preceded first by observations of transcriptional inhibition by antisense RNA expressed in transgenic plants and more directly by reports of unexpected outcomes in experiments performed by plant scientists in the U.S. and The Netherlands in the early 1990s. Andrew Fire and Craig Mello published their break-through study on the mechanism of RNA interference in Nature in 1998. It was earlier known that antisense RNA23, but remarkably also sense RNA24 could silence genes, but the results were inconsistent and the effects usually modest. However, due to the fact that both sense and antisense RNA could cause silencing Mello argued that the mechanism could not just be a pairing of antisense RNA to mRNA, and he coined the term RNA interference for the unknown mechanism.