small interfering RNA

Small interfering RNA, abbreviated siRNA, is a short molecule made of the cellular substance RNA — the chemical relative of DNA that transports information within cells. An siRNA consists of two paired strands and is only about 21 to 23 building blocks long. Its task is to intercept a very specific message in the cell and destroy it before it is converted into a protein. This allows it to specifically silence a single gene. This mechanism is called RNA interference — the siRNA literally disrupts the cell’s flow of information.

siRNA as a tool against disease genes

Many diseases arise because a gene produces too much or the wrong thing. Classic drugs usually target the finished protein — the gene’s end product. siRNA intervenes earlier: it prevents the protein from being produced in the first place. This is more precise, because in theory a matching siRNA can be designed for any given gene.

siRNA is also an indispensable tool for research. Scientists use it to switch off genes in cells in order to understand what function they have. Instead of creating a gene mutation — which is laborious — it is enough to introduce the matching siRNA into the cell. The effect is temporary and therefore controllable.

How siRNA destroys a message

Genes are stored in DNA, but cells do not read them directly. First, an intermediate molecule is produced, the so-called messenger RNA (mRNA). This mRNA carries the blueprint for a protein. This is exactly where siRNA intervenes: one of its two strands searches for the mRNA with the matching sequence — like a key that only fits one particular lock.

If the strand finds its target, it binds to it. A protein complex in the cell, called RISC, recognizes this connection and cuts the mRNA apart. The blueprint is thereby destroyed. Since the mRNA is missing, the protein cannot be built — the gene is silenced. The RISC then detaches again and can go on to destroy further mRNA molecules of the same type. A single siRNA can therefore act multiple times.

The most difficult part is not designing the siRNA, but delivering it. RNA molecules are broken down quickly in the blood. Researchers therefore package siRNA into tiny fat coatings, so-called lipid nanoparticles, which transport it safely into the target cells. This very technology was also used in mRNA vaccines against COVID-19.

siRNA in approved drugs and current debates

siRNA is not a technology of the future — several approved drugs based on it already exist. Inclisiran, for example, lowers cholesterol levels by switching off a gene in the liver that produces too much LDL cholesterol. It is injected only twice a year, because its effect lasts that long. Patisiran was approved in 2018 as one of the first siRNA drugs worldwide and treats a rare disease of the nervous system.

In tech and biotech news, siRNA mainly appears in connection with investments in RNA therapies. Pharmaceutical companies are competing over which disease will be targeted next with an siRNA treatment — cancer, rare genetic diseases, and cardiovascular diseases are at the top of the list. The technology is considered one of the most promising approaches in modern medicine, because in principle it can be applied to any gene in the human cell.

A common misconception is to equate siRNA with gene editing such as CRISPR. CRISPR permanently alters DNA. siRNA changes nothing — it only switches off temporarily. The DNA remains untouched. This makes siRNA less powerful, but also less risky.