RNA interference, also known as RNAi, is a biological response mechanism that can “interfere” with the central dogma of biology – genes are “expressed” when they are copied into messenger RNAs (mRNAs) that can be “translated” into functional proteins. By interfering with specific mRNAs, the natural biologic process of RNAi can reduce the production of a target protein.

How RNAi Works

RNAi is a natural mechanism used by your cells to regulate expression of genes and defend against viruses by interfering with viral RNA. A key component of RNAi is the RNA-Induced Silencing Complex (RISC). Your cells contain a multiprotein complex called RISC which selectively targets mRNAs for degradation. 

Naturally occurring siRNAs can be incorporated into RISC and mediate degradation of targeted mRNAs. Similarly, delivery of specifically designed therapeutic interfering RNAs to appropriate cell types can also enable rational silencing of genes.

Therapeutic RNAi in Action

Many diseases are caused by genes that make a dysfunctional protein (or too much of a normal protein). Arrowhead can harness RNAi to silence specific mRNAs and reduce the production of proteins that cause disease. While traditional small molecule drugs are often only effective against limited families of disease-causing proteins, by targeting mRNA directly therapeutic RNAi can target any disease-causing protein, thereby increasing the number of potential drug targets.

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