siRNA

An siRNA, short for small interfering RNA, is a tiny double-stranded RNA drug that tells a cell to shred a specific message before it can be used. Cells already have a built-in shredding crew for unwanted RNA; an siRNA hands that crew a precise wanted-poster so it knows exactly which messenger RNA to destroy.

Mechanically, the double strand is loaded into a protein complex called RISC. One strand is discarded; the remaining guide strand steers RISC to any messenger RNA with a matching sequence, and an enzyme in the complex cuts that RNA. Because RISC is catalytic and reused, one siRNA can knock down many copies of the target, often giving long-lasting gene silencing.

Like other oligonucleotides, siRNAs need chemical armor and a delivery system to reach cells. A common trick is attaching a sugar tag called GalNAc that ushers the drug into liver cells, or packaging it in a lipid nanoparticle. Their advantage over antisense is catalytic potency; their limit is that delivery beyond the liver is still hard.